Richard's Venture to China for Stem Cell Therapy

A recent article on stems cells in China

2010-05-28T23:40:00.000-07:00

Apparently there are people who read this blog. Here's an article from the Milwaukee-Wisconsin Journal Sentinel dated February 1, 2010:

The Cell Peddlers: Dealing Hope to Desperate Families
Sorting out the sales pitch

The Internet has helped companies spread the word of 'miracle' recoveries, but families have to tread carefully

By Meg Kissinger of the Journal Sentinel
Posted: Feb. 1, 2010
Second of two parts

Megg Lasswell was writing a blog entry about her baby daughter's vision problems when an intriguing message popped on the screen.

Her daughter, GiGi, was born with optic nerve hypoplasia, making her able to see only blurry outlines and shapes. The message read:

"I can treat your child's ONH. You can look me up on the web if you like. My name is Kirshner Ross-Vaden and I work for a bio-tech company. Check out www.stemcellschina.com and www.beikebiotech.com. It is real. My email is kirshner@beikebiotech.com. I hope to hear from you. K"

Curious, Lasswell e-mailed Ross-Vaden for more details, but any hopes she had that the treatments would work faded. Over the course of the next several weeks, she learned that it would cost $30,000 or more for an unproven stem cell procedure with no reasonable hope of a cure.

Lasswell was livid.

"It's obvious now that these people don't care about our families," she said in her blog. "They are using a support group to offer people the world, or at least vision for their children. How cheap and disgusting is that?"

The company behind the unsolicited e-mail was Beike Biotechnology, a China-based enterprise that claims to be able to treat cerebral palsy, autism, spinal cord injuries, optic nerve disorders and two dozen other conditions with stem cells. Scientists say the treatments rely on flawed theories, have not been vetted to tell if they will make any difference and amount to patients paying to be subjects of an experiment.

Just as scientists are critical of Beike's medical claims, marketing experts say the company uses questionable tactics, relying on patient testimonials that are difficult - if not impossible - to verify. It tries to lure customers by using emotional accounts from those who have the most at stake: Patients and their families who have often solicited the financial support of a community hungry for happy endings.

With its aggressive approach, Beike (pronounced Bay-Ka) has built itself into one of the largest stem cell companies in the world. It has done so by using the Internet to spread one unchecked "miracle" story after another, like a modern-day game of telephone. With each retelling, the stories and their alleged results get a little more fantastic.

As part of its examination of Beike, the Journal Sentinel built a database of all the patients listed on the company's Web site. Reporters contacted more than two dozen of them to see how they learned of Beike and what their experiences with the company were. The newspaper found:

• Unsolicited contact: The company's marketing agents troll the Internet looking for families desperate for cures and offer them unrealistic medical outcomes. In one case, a representative quoted a 98% improvement rate for an unproven treatment, which scientists call outrageous.

Alex Moffett, chief executive officer of Beike's holding company, said that recruiters' tactics and claims are "impossible to control" and that Beike "obviously cannot police all such activities."

• Inaccurate information: The company perpetuates inaccurate or unsubstantiated information about the treatments on its Web site by linking to scores of newspaper and TV stories. These emotional accounts often lack any substantiation from doctors or scientists. The stories then entice others to seek Beike's treatments. The company does not list unfavorable stories that challenge the effectiveness of its treatments.

• Hidden ties: Beike's marketing agents, also called "facilitators" or "medical liaisons," funnel patients into a sophisticated system that provides help in raising money, making travel arrangements to China, securing passports, even wiring money to China to pay for the treatment. Some company agents have exaggerated their expertise and offered confusing descriptions of their relationships to the company.

Nevertheless, hundreds of families - including several from Wisconsin - have each spent tens of thousands of dollars on these treatments in recent years, often defying their doctors' advice and eliminating their chance to participate in rigorous clinical trials in the United States.

"Plenty of companies use the Internet to find customers," said Susan Lederer, chairman of the department of medical history and bioethics at the University of Wisconsin-Madison. "But it seems particularly sleazy to take advantage of those who are desperate. These are people who are under stress. They are especially vulnerable to this hucksterism."

Moffett defended his sales staff and said he had little control over how they seek clients.

"Our young international staff members are passionate about stem cell therapies," he wrote in an e-mail to the Journal Sentinel. "They are on the Internet many hours a day and have expressed personal comments and are involved in various levels of interaction with blogs and other forums for comment and discussion. Beike feels this is their right to communicate as they wish."

More than two years after Lasswell was contacted by Beike, her daughter's sight is improving on its own. But Lasswell remains angry at the solicitation from Ross-Vaden.

"It was gross the way that she fished the Internet looking for me," said Lasswell, of Oakland, Calif.

Although Ross-Vaden said in her overture to Lasswell that she could treat her daughter's condition, Ross-Vaden is not a doctor or research scientist. Ross-Vaden said she developed Beike's protocol for treating the disease, but company officials deny that.

She says she is a registered nurse, but will not say where she is licensed.

The Journal Sentinel interviewed Ross-Vaden last year at her home in suburban Chicago. She refused to provide key information, such as where she received her degree, and did not want the name of her community mentioned.

"I've been harassed and threatened too many times," she said.

Ross-Vaden said that when she solicited Lasswell in 2007, she was working for Beike as vice president of the company's foreign patient division and she regularly traveled to China to help set up and supervise the treatments.

But Moffett said Ross-Vaden was not an employee. Rather she was paid a commission for each patient she referred.

However, Ross-Vaden said she was paid a straight salary and declined Beike's offer of a commission for new patients.

"I didn't feel comfortable taking a percentage," she said.

Ross-Vaden said she quit the company in March 2009 because she wanted to try to have another baby. She continues to recommend Beike to people she meets on the online chat room she supervises from her house.

Ross-Vaden said she became interested in stem cell treatments when her son, Justin, was born with significant brain injuries and received stem cell treatments in Mexico. He died four years ago at the age of 2.

She said she found Lasswell by setting up a program on her computer that would alert her to any stories or blog entries about certain diseases. She was surprised to hear of Lasswell's criticism.

"I'm offering hope," Ross-Vaden said. "No one has to take it."

When a patient signs on to pay for treatments, Beike often assigns a facilitator, also known as a medical liaison.

The company sets up blogs for its patients and encourages them to write about their time in China so that others can see how the treatment is going.Once patients are home, Beike officials follow the blogs to ensure they provide a positive spin, according to some patients.

Richard Chin went to China in March 2007 for stem cell injections to treat ataxia, a disease of the nervous system.

Soon after he returned home, his wife wrote on their blog that Chin was scheduled to see his doctor for a post-treatment consultation. The blog also mentioned Chin had recently sprained his foot.

Three days before the scheduled doctor's appointment, the couple got an e-mail from Jon Hakim, then a Beike official, asking Chin to postpone the visit for another week.

Hakim referenced the foot injury and told them he wanted Chin to see the doctor on "an up day instead of a down day."

Chin's wife, Lilly Lock, was left feeling that Beike employees were monitoring what they wrote to affect the outcome of his medical examination.

"I cannot shake the feeling that Big Brother is watching," Lock wrote on the blog. "Is Jon using our blog to monitor us? I'd like to believe that he is interested in Richard's health as a friend and not as a salesperson of stem cell treatment. However, some of his requests can be construed as too self-serving."

Hakim also asked the couple to remove from their blog a link to a Wall Street Journal article that was critical of the company.

Hakim, who quit his job at Beike late last month, said he "asked nicely that they wait a little while" until Chin was feeling better.

"It's usually best to have the patient go in before and after evaluations in a similar state to get a real feel for the effects of the treatment."

Hakim said he left the company to take a job at a wireless start-up in China.

Beike markets itself aggressively on the Internet, such as with a flier that circulated before Christmas 2008:

"Join us in China to celebrate the holidays and we will wrap up 15 million little gifts to go under your tree for free! . . . Book to arrive in China and receive treatment in the month of December and you will receive a free stem cell transplant with approximately ten to fifteen million stem cells."

Smaller print explained: "certain restrictions do apply."

MEDIA ACCOUNTS

Many patients, though, find Beike through glowing stories in their local media.

Brandon Meinke of Janesville has Type 2 spinal muscular atrophy, a degenerative and potentially crippling disease. A relative sent his grandparents a story from Florida about a boy who had gone to Beike for stem cell treatments.

"We went on their Web site and saw all of these stories, and we felt like we had to try," said Sharon Vaughan, Brandon's grandmother.

In September 2008, a local TV station and the local newspaper ran stories on Brandon's upcoming trip. The newspaper story paraphrased a statement from Brandon's grandfather, Ron Martin: "There is no cure for Brandon's disorder, but other patients are proving the stem cell injections stop the progression."

Medical experts in spinal muscular atrophy say there is no such proof.

"I would argue there is absolutely no data to indicate cord blood will help with spinal muscular atrophy," said Stephen Minger, a British stem cell scientist who has studied the disease. "I can't imagine what it is that cord blood will do to help reverse that. . . . It is just ridiculous to believe that this is going to work."

When Kyle Knopes, a Janesville teenager with the same condition, read about Brandon, his hopes soared.

Kyle, now 17, was diagnosed as a baby with the condition. He had used a wheelchair since he was 18 months old. Conventional treatments weren't slowing the disease. By the time Kyle was 15, his neck muscles were too weak to support his head, and his fingers were starting to curl, making it difficult to hold a fork.

Kyle's doctor advised him and his family not to go, but by the following summer, in August 2009, Kyle and his mother and brother were off to China. They sent the company $27,500 and while they were in China, Kyle's father wired $3,500 for another injection. Kyle said he's greatly improved since he returned, having received eight injections of umbilical cord stem cells. He can hold his head up, grip a pen and even roll from side to side, something he said he hadn't been able to do in years.

But no doctor has measured Kyle's progress since he returned.

A handful of American doctors who have examined Beike patients before and after treatments for different conditions told the Journal Sentinel that they saw no change. In some cases, patients have reported fleeting improvements - and when they regress, Beike has used it as an opportunity to sell them another round of therapy.

Stem cell experts say the improvements patients report could be a placebo effect.

"Some patients report these kind of 'dramatic' improvements, but generally they don't last," said Minger, who is director of the stem cell biology lab at King's College in London.

Kyle said he doesn't care what other people think about whether these treatments work or not.

"I know what I could do before and what I can do now," he said. "It doesn't matter what people think or say about the treatments I got. How I feel is all that matters."

He now travels to schools around Janesville talking about the benefits of stem cell treatments, and stories about him are now among those promoted on Beike's Web site.

"I just had a woman from Canada call," Kyle said recently. "I think she's going to go."

Journalism ethics experts say reporters have to be careful not to play into the company's claims or they risk becoming unwitting barkers for an unproven product.

"Otherwise, we're back to the days of selling snake oil on the streets," said Stephen Ward, a professor of journalistic ethics at the University of Wisconsin-Madison.

"Studies show that the public makes medical decisions on what they see in the media," he said. "People who are sick want hope. They are ripe for being used. The chief journalistic rule is to be skeptical, check it out. A feel-good miracle story doesn't overcome a reporter's need to verify.

INTERNET SEARCH

Increasingly, people look to the Internet for health information, said Susannah Fox of the Pew Research Center in Washington, D.C. But many people aren't discriminating enough about the information they find there, she said.

The Internet is a source of power for people, particularly those who feel powerless against an incurable disease, Fox said.

"People facing medical crises want to become superheroes," she said. "They want to save a life. They believe the answer is out there if they can find it. "

Federal Trade Commission rules prohibit a company from making false claims on the Internet. But enforcement can be difficult when the company is based in another country, said Richard Cleland, an FTC spokesman.

He declined to say whether the FTC has had complaints about Beike.

Of all the cases that the Journal Sentinel reviewed, none got more public attention than that of Macie Morse.

The 16-year-old from northern Colorado went to China in the summer of 2008 for treatment of optic nerve hypoplasia.

She and her mother are claiming a miracle.

But the ophthalmologist who examined her before and after the treatments could find no improvement, said Macie's mother, Rochelle Morse. And experts in optic nerve hypoplasia said children with the condition often experience improved vision without any treatment at all.

Whatever the reason, Macie's eyesight has improved enough that she was granted a driver's permit last March.

However, the permit requires that she wear glasses specially fitted with a binocular-like device that allows her to see the lines on the road. In school, she requires a telescope to see the blackboard.

When Macie was featured on television news shows throughout Colorado after she got her driver's permit, she was not shown wearing the glasses and no mention was made of them.

"This is crazy!" Macie exclaims in one broadcast, as she drives the van down the street.

Shaun Boyd, a television reporter from Denver riding with her, says: "Crazy in a miracle-can-happen way."

Boyd, a reporter for CBS4 in Denver, said she didn't remember whether anyone told her Macie needed to wear the special glasses to drive.

"This is TV," Boyd said. "We drove around the block. It's not like I asked her not to wear the glasses so that we'd have a better shot or anything like that."

Rochelle Morse told the Journal Sentinel they weren't trying to fool viewers. She said Macie did not wear her glasses because it was only a short drive.

Beike officials said it should not be an issue.

"Regardless of why she was photographed like this, what a miracle for this child!" said Moffett. "It seems silly to try and find fault with such a wonderful outcome and the obviously life transformative benefits for her and the family."

Rochelle Morse organized an online chat room where she urges all who are considering it to go to China for the treatments. She also organizes medical awareness rallies to tout the benefits of the treatments.

At one such rally last year in Florida, Macie was the most anticipated speaker. She told the crowd that vision in one of her eyes has gone from 20/400 to 20/80.

"I saw snow fall for the first time," she told the crowd.

When asked to document Macie's improvement, Beike officials offered months ago to provide the Journal Sentinel with her medical records. They have not done so despite repeated requests.

Beike has compensated Macie's family for such testimonials with free transportation around China - a fact not mentioned at the rally.

Having spent $30,000 the first time, the family is getting ready to go back sometime this month for more treatment, hoping for still more improvement.

Rochelle Morse said in an interview she will ask the company for a discount for their upcoming trip for more treatments because of all the publicity the family has generated for the company.

At the rally, she had a message for the skeptics.

"It's not the placebo effect," she said, "and if it is, screw them. It works."

HOW UNVERIFIED CLAIMS ARE SPREAD

• Ron Martin, whose grandson, Brandon, suffers from Type 2 spinal muscular atrophy, gets a story from a Florida newspaper about a patient with the same disease who went to China for Beike's stem cell treatments. They, too, plan a trip to China.

• In September 2008, the local newspaper runs a story on Brandon's trip to China for the treatments, quoting Martin that stem cells are proving to stop the disease. Local TV stations also do stories.

• Kyle Knopes, who has the same disease, reads the story and calls Martin for more information. He plans a trip, too.

• The company, trading on the credibility of the media outlets, posts the stories on its Web site.

RALLYING CRY

In March 2009, a Journal Sentinel reporter attended a stem cell awareness rally in Punta Gorda, Fla., organized by a supporter of Beike Biotechnology.

The event, held in a gazebo overlooking Charlotte Harbor, brought together both prospective and former patients, including children who had received treatment from Beike for optic nerve hypoplasia. About 75 people attended.

Those in the crowd included Beike officials and others, purporting to be independent, whose actual roles and relationships to the company were not made clear. One example:

One of the speakers was Ali A. Hakim, introduced as an expert in stem cells.

Hakim, 82, a urologist who lives in Minnesota, is the father of Jon Hakim, then Beike's marketing director.

Ali Hakim gave a talk praising the company's work, but was vague when asked about his relationship to the company: "I have been working with them for four years. I don't work for them. I don't take one penny."

However, the event's organizer, Carol Petersen, whose grandson was treated by Beike, described herself as a salaried employee of Ali Hakim.

"He's part of them," she said of Hakim, "but I wouldn't call him a Beike employee."

Mark Johnson, the reporter from the Journal-Sentinel, who contacted us in January of this year for this article wrote the first part of this series here.

CBS 60 Minutes April 18, 2010

2010-04-17T22:27:00.000-07:00

Watch this program Sunday (April 18, 2010) evening at 7PM. (EST) The producer of this segment, Sam Hornblower, interviewed Richard by phone while he was gathering information on the subject of stem cell treatments. No, Richard does not have any "air time" on the program.

Click here for more information on this program.

THE NATIONAL ATAXIA FOUNDATION 53RD ANNUAL MEMBERSHIP MEETING

2010-01-18T13:47:00.000-08:00

Happy New Year! I'm happy to report that Richard is doing well and adhering to his PT and exercise regime. His appetite is good and his choking spells infrequent.

We recently received an email about the National Ataxia Foundation (NAF) Annual Membership Meeting 2010 and would like to share it with you. The meeting will be held in Chicago from March 12th to 14th, 2010. We have attended the annual meetings for the last two years and have enjoyed them tremendously.

Here's the link with more information:

http://www.ataxia.org/events/annual-meeting2010.aspx

Stem Cell Tourism Revisited

2009-10-10T12:54:00.000-07:00

We received an email from Jane Qiu today about her recently published article in the September 2009 issue of Nature Biotechnology. Jane had interviewed Richard in 2007 about his stem cell therapy experience in China which resulted in an article published by the Lancet Neurology in February 2008.

The Nature Biotechnology article which is entitled "Trading on Hope" is a followup to her investigation of "the thriving business of selling stem cell transplants as cure-alls for debilitating diseases." Jane has graciously made available a copy of her article to us.

Please click on the link, TradingonhopeNatureBiotech9-09.pdf, here.

Furthermore, Jonathan Kimmelman, who holds a PhD in Molecular Biophysics and Biochemistry from Yale University and is currently with the Biomedical Ethics Unit Faculty at the McGill University in Montreal, Canada, commented on Jane's article in his blog (Lost in Translation) post of September 23, 2009.

Perchance to dream

2009-10-02T00:48:00.000-07:00

On our last visit with Dr. Susan Perlman at UCLA, Richard had complained about how he was suffering from parasomnia. He has experienced, on a regular basis, night terrors, sleep talking, bruxism and periodic leg movement. He has even fallen out of bed several times as a result of his nightmares. Needless to say, the quality of his sleep was less than satisfactory in general.

After consulting with her colleague, Dr. Perlman prescribed melatonin, which is OTC, to address the issue. We are happy to report that after taking this drug for a few months, the symptoms have abated. He is now sleeping more soundly which in turn translates to more energy during the day.

I continue to be gratified by how Dr. Perlman is able to tackle problems that plague Richard and other MJDers by using existing drugs or supplements. For example, melatonin is used mainly to help with circadian rhythm disorders like jet-lag disorders. Similarly, she suggested Fluoxetine (trade name Prozac) to help Richard with swallowing and choking problems and that too has worked well in the last two years. I hope and believe that there are many more drugs and supplements out there that one day will be shown to be equally effective in treating various MJD symptoms.

The latest research on MJD/SCA3

2009-09-30T15:39:00.000-07:00

Here's an article from PloS ONE where researchers are trying to understand the behavior and movement of material of the nucleus (center) of the cell of someone who has MJD. Ataxin-3, I believe is the mutated genetic material within an MJDer's body cells that causes the ataxia. With a clearer picture as to how the "bad stuff" gets transported into the cells, the researchers can then think of and experiment with different ways in preventing that from happening.

It is a very technical article. I am nowhere close to even understanding 10% of what is written. Nevertheless, for those who are interested in learning more about this subject, here is the article in its entirety:

PLoS ONE. 2009; 4(6): e5834.
Published online 2009 June 8. doi: 10.1371/journal.pone.0005834.

PMCID: PMC2688764
Copyright Macedo-Ribeiro et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Nucleocytoplasmic Shuttling Activity of Ataxin-3
Sandra Macedo-Ribeiro,#1* Luísa Cortes,#2 Patrícia Maciel,3 and Ana Luísa Carvalho2,4*
1IBMC-Instituto de Biologia Molecular e Celular, Universidade do Porto, Porto, Portugal
2Center for Neuroscience and Cell Biology (CNC), University of Coimbra, Coimbra, Portugal
3Life and Health Sciences Research Institute (ICVS), School of Health Sciences, University of Minho, Braga, Portugal
4Department of Zoology, University of Coimbra, Coimbra, Portugal
David C. Rubinsztein, Editor
University of Cambridge, United Kingdom
#Contributed equally.
* E-mail:sribeiro@ibmc.up.pt (SMR);Email: alc@cnc.cj.uc.pt (ALC)
Conceived and designed the experiments: SMR PM ALC. Performed the experiments: LC ALC. Analyzed the data: SMR LC ALC. Contributed reagents/materials/analysis tools: PM. Wrote the paper: SMR LC ALC.
Received March 4, 2009; Accepted May 8, 2009.
Top
>Abstract
Introduction
Methods
Results and Discussion
References

Abstract
Spinocerebellar ataxia type-3, also known as Machado-Joseph Disease (MJD), is one of many inherited neurodegenerative disorders caused by polyglutamine-encoding CAG repeat expansions in otherwise unrelated genes. Disease protein misfolding and aggregation, often within the nucleus of affected neurons, characterize polyglutamine disorders. Several evidences have implicated the nucleus as the primary site of pathogenesis for MJD. However, the molecular determinants for the nucleocytoplasmic transport of human ataxin-3 (Atx3), the protein which is mutated in patients with MJD, are not characterized.
In order to characterize the nuclear shuttling activity of Atx3, we performed yeast nuclear import assays and found that Atx3 is actively imported into the nucleus, by means of a classical nuclear localizing sequence formed by a cluster of lysine and arginine residues. On the other hand, when active nuclear export was inhibited using leptomycin B, a specific inhibitor of the nuclear export receptor CRM1, both endogenous Atx3 and transfected GFP-Atx3 accumulated inside the nucleus of a subpopulation of COS-7 cells, whereas both proteins are normally predominant in the cytoplasm.
Additionally, using a Rev(1.4)-GFP nuclear export assay, we performed an extensive analysis of six putative aliphatic nuclear export motifs identified in Atx3 amino acid sequence. Although none of the tested peptide sequences were found to drive nuclear export when isolated, we have successfully mapped the region of Atx3 responsible for its CRM1-independent nuclear export activity. Curiously, the N-terminal Josephin domain alone is exported into the cytoplasm, but the nuclear export activity of Atx3 is significantly enhanced in a longer construct that is truncated after the two ubiquitin interaction motifs, upstream from the polyQ tract.
Our data show that Atx3 is actively imported to and exported from the cell nucleus, and that its nuclear export activity is dependent on a motif located at its N-terminal region. Since pathological Atx3 aggregates in the nucleus of affected neurons in MJD, and there is in vivo evidence that nuclear localization of Atx3 is required for the manifestation of symptoms in MJD, defects in the nucleocytoplasmic shuttling activity of the protein may be involved in the nuclear accumulation and aggregation of expanded Atx3.
Top
Abstract
>Introduction
Methods
Results and Discussion
References

Introduction
Machado-Joseph disease (MJD), or spinocerebellar ataxia type 3, is the most common dominantly inherited ataxia worldwide and it is caused by a polyglutamine (polyQ) expansion in ataxin-3 (Atx3), a polyubiquitin-binding protein [1] with ubiquitin protease activity [2]. Full-length Atx3 contains an N-terminal Josephin domain (JD), the conserved catalytic module, two ubiquitin interacting motifs (UIMs), an expandable polyQ stretch, and a short variable tail that might contain a third UIM depending on the splice variant [3]. In normal individuals the size of the polymorphic glutamine repeat can range between 14 and 40 while in MJD patients the polyQ repeat is expanded to 53 or more glutamines [4]. Human Atx3 is ubiquitously expressed and displays a complex subcellular distribution involving both the cytoplasm and the nucleus, depending on cell type [5], [6], [7]. Even though its physiological role is still not clearly established, Atx3 was shown to be a cysteine protease with the ability to cleave polyubiquitin chains with more than four ubiquitins, independently of the polyglutamine tract [2]. This enzymatic activity of Atx3 has been correlated with its ability to mitigate polyQ-induced neurodegeneration in a Drosophila model [8], with its involvement in aggresome formation [9] and in the degradation of misfolded proteins [10]. Furthermore, it was also shown to bind to histones [11] and to chromatin [12] indicating that Atx3 displays not only cytoplasmic but also nuclear functions.
As for most other polyQ diseases, conformational changes imparted by the expanded polyQ tract lead to the formation of neuronal intranuclear inclusions (NIIs) [13] and may contribute to pathogenesis by affecting gene expression [14] or by disrupting nuclear organization and function [15]. In MJD patients specific brain regions are affected such as the cerebellum and brainstem, with prominent cell loss in the pontine and dentate nuclei [6], [16], [17]. It is becoming clear that although polyQ tracts themselves are toxic, the sequence and structure of the proteins carrying the polyQ tracts have important roles in defining the course and specificity of the disease. Those sequences determine subcellular localization, and specify interactions with other macromolecules within the cell, strongly determining the differences in the specificity of neuronal degeneration characteristic of polyQ disorders [18], [19], [20].
A contentious question has been whether polyQ-induced pathogenesis is primarily activated in the cytoplasm or in the cell nucleus. In fact predominantly nuclear inclusions have been found in SCA1, SCA2, SCA7, SCA17, DRPLA, SBMA, and Huntington's Disease (HD) patients [21], although cytoplasmic inclusions have also been identified in affected brain regions in SCA2 [22] and HD [23]. Evidence from HD transgenic mice shows that both nuclear and cytoplasmic exon-1 huntingtin might contribute to disease progression [23], [24], [25]. Nuclear environment has been shown to favor toxicity, pathology and aggregation as evidenced by nuclear targeting of polyQ peptides [26], even when inserted into ectopic protein contexts [27].
Specific nuclear localization sequences (NLS) have been identified in proteins carrying the expanded polyQ tracts, such as ataxin-1 [28], [29] and ataxin-7 [30], and nuclear-associated mechanisms are being implicated in neuropathogenesis [13], [31]. Similarly, nuclear export sequences (NES) have been found in ataxin-7 [32] and huntingtin [33] and it was shown that polyQ expansion impairs efficient nuclear export of these polyQ-containing proteins [32], [34].
Recently, it was demonstrated in vivo that adding an exogenous NLS to Atx3(148Q) increases the severity of the phenotype and induces earlier death in transgenic mouse models [35]. Accordingly, adding an exogenous NES to Atx3(148Q) drives the expanded protein out of the nucleus and prevents the manifestation of a phenotype [35]. This suggests that defects on the nucleocytoplasmic shuttling activity of the expanded protein might be correlated with pathology and neuronal specificity. Moreover, in other transgenic models of Machado-Joseph disease there is accumulation of the expanded Atx3 protein in the nucleus of affected neurons [36], [37], [38]. However, the molecular determinants for the nucleocytoplasmic transport of Atx3 are not characterized. In order to gain further insights into the function of Atx3 and into the disease-specific mechanisms of neurodegeneration in MJD, we have set as our goal the identification of the determinants of Atx3 nucleocytoplasmic transport.
Nuclear targeting was analyzed in vivo using the yeast system developed by Rhee et al. [39] and we found that Atx3 is actively imported into the nucleus, by means of a classical NLS located in its C-terminal region. Furthermore, using an in vivo nuclear export assay we show that Atx3 is actively exported from the nucleus and mapped this export activity to its N-terminal domain.
Top
Abstract
Introduction
>Methods
Results and Discussion
References

Methods
Yeast nuclear import assay
The yeast nuclear import assay was performed as described previously [39]. The cDNA encoding the MJD1.a isoform of ataxin-3 (AAB33571), containing 28 CAG repeats, was amplified by PCR using the pEGFP-C1-ataxin-3(28Q) construct (kindly provided by Dr. Henry Paulson) as template and using the primers 5′tcccccgggcatggtgagcaagggcg3′ and 5′gcgtcgacttatgtcagataaagtgtgaag3′, which introduced SmaI and SalI recognition sites at the 5′ and 3′ ends of the amplified DNA fragment, respectively. The cDNA encoding ataxin-3(28Q) was cloned into the SmaI and SalI sites of the plasmid for the yeast nuclear import assay (pNIA, kindly provided by Vitaly Citovsky [39]), and named pNIA-GFP-Atx3. The pNIA-GFP-Atx3R282T and pNIA-GFP-Atx3R282A constructs were obtained by site-directed mutagenesis (QuickChange site-directed mutagenesis kit, Stratagene).
The pNIA constructs, encoding triple fusion proteins comprising bacterial LexA, yeast Gal4p activation domain (Gal4AD), and the tested protein, were transformed using the lithium acetate method [40] into Saccharomyces cerevisiae L40 strain, which contains the reporter genes HIS3 and lacZ with upstream LexA operators. After transformation, yeasts were plated on selective medium deficient for tryptophan, to select for transformed cells. Transformed yeasts were then plated on selective medium lacking both tryptophan and histidine, and supplemented with 100 mM 3-amino-1,2,4-triazole (3AT; Sigma), an inhibitor of the His3p enzyme, and growth was evaluated. Additionally, transformed yeasts were grown in tryptophan-deficient liquid medium for quantitative determination of β-galactosidase activity [41]. For the enzymatic assay, cells were disrupted, and the β -galactosidase substrate o-nitrophenyl-β-D-galactopyranoside (ONPG) was added in excess. The reaction occurred at 30°C and was stopped by raising the pH to 11. The optical density of the reaction product was measured at 420 nm (OD420), and the β-galactosidase activity was calculated according to the following equation: βunits = 1,000×OD420/t×V×OD600, where OD420 is the optical density at 420 nm of the sample measured after the incubation of yeast cell lysate with ONPG, t is the time of incubation (in minutes) of the yeast cell lysate with ONPG, V is the volume of the sample used in the assay (in milliliters), and OD600 is the optical density at 600 nm of the yeast cell culture at the start of the assay.
Cell culture, transfection and leptomycin B treatment
HEK293 and COS-7 cells were grown and maintained in Dulbecco's modified Eagle's medium-high glucose (DMEM-HG; Sigma) supplemented with 10% (vol/vol) heat-inactivated fetal bovine serum (FBS; Biochrom KG) and with 100 U of penicillin and 100 µg of streptomycin (Sigma) per ml in a 5% CO2 humidified atmosphere at 37°C.
One day prior to transfection, COS-7 cells were seeded onto glass coverslips on a 12-well plate, at a subconfluent density. Transfection experiments were performed using Lipofectamine reagent (Invitrogen) according to the manufacturer's instructions, using 1 µg of plasmid DNA per well. The cells were incubated for 48 hours to allow gene expression.
Where indicated, the cells were incubated with 20 ng/ml leptomycin B (Sigma) in DMEM-HG supplemented with 10% FBS for 3 hours prior to fixation.
Rev(1.4)-GFP nuclear export assay
To assess the strength of the nuclear export activity of different fragments of Atx3 protein, or of full-length Atx3, the Rev(1.4)-GFP nuclear export assay, described previously by Henderson and Eleftheriou [42], was used. This assay is based on the manipulation of the Rev protein shuttling cycle, and tests for the ability of functional nuclear export sequences to promote the nuclear export activity of the Rev(1.4)-GFP fusion protein, which is composed of a NES-deficient mutant of the HIV-1 Rev protein and GFP.
Potential Atx3 NES signals were identified by consensus to the ΦX1–3ΦX2–3ΦXΦ motif (Φ indicates a large hydrophobic residue, and X indicates any amino acid), and using the prediction algorithm NetNES (http://www.cbs.dtu.dk/databases/NESbase-1.0 [43]), and fused to Rev(1.4)-GFP fusion protein (the plasmid encoding Rev(1.4)-GFP was kindly provided by Beric R. Henderson). The putative sequences that were assayed include: NES1, residues 76-SIQVISNALKVWGLELILF-94; NES2, 133-LNSLLT-138; NES3, 142-LISDTYLALFLAQLQQE-158; NES4, 174-ADQLLQMIRV-183; NES5, 209-LERVLE-214; and NES6, 222-LDEDEEDLQRALALSRQEIDME-243. Furthermore, full-length Atx3 (28Q and 84Q) or partial domains of Atx3 (the Josephin domain and the domains comprising amino acids 1–263 and 183–263) were also fused to Rev(1.4)-GFP fusion protein.
COS-7 cells were transfected with pRev(1.4)-GFP (negative control) or its derivative plasmids containing either the NES of the HIV-1 Rev protein (positive control) or each of the sequences to be tested. Forty-eight hours post-transfection, all cell samples were treated with 10 µg/ml cycloheximide (CHX) to ensure that any cytoplasmic GFP fluorescence resulted only from the nuclear export of GFP fusion proteins and not from de novo protein synthesis. Simultaneously, part of the cell samples were also treated for 3 hours with 5 µg/ml actinomycin D (ActD), which is known to specifically block the nuclear import of Rev protein by a mechanism not yet elucidated [42]. The remaining cell samples were treated with CHX, ActD and 20 ng/ml of leptomycin B for 3 hours. The subcellular localization of each GFP fusion protein was determined in at least 200 cells per experimental condition from three independent experiments.
Fluorescence microscopy
Endogenous Atx3 was detected, by immunocytochemistry, with anti-MJD antibody (1[ratio]10000), kindly provided by H. Paulson, and visualized using a secondary antibody labeled with Alexa 488 (1[ratio]1000, Invitrogen). For fluorescence analysis of GFP fusion proteins, cells were washed with phosphate-buffered saline (PBS), fixed with 4% paraformaldehyde: 4% sacarose for 15 min, and rinsed with PBS. The coverslips were then inverted and mounted on glass slides with Vectashield mounting medium (Vector Laboratories). The cell nucleus was stained with Hoescht 33342 (0,5 µg/ml, Molecular Probes). Fluorescence observations were performed using a Zeiss Axiovert 200 fluorescence microscope, coupled to a digital photographic camera (Axiocam HRM). Confocal microscopy was performed using a Zeiss LSM 510 Meta system.
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Abstract
Introduction
Methods
>Results and Discussion
References

Results and Discussion
Ataxin-3 has a mixed cytoplasmic and nuclear distribution
Ataxin-3 is an ubiquitous protein that is found both in the cytoplasm [44] and in the nucleus [5], [7]. However, upon expansion of the polyQ tract the protein forms insoluble inclusions predominantly located inside the nucleus of the affected cells [6]. Interestingly, the localization of the protein inside the cell is critically dependent on the cell type [5], [7]. Immunostaining of HEK293T cells with an anti-Atx3 antibody (kindly provided by H. Paulson [6]) showed that endogenous Atx3 is predominantly located in the nucleus (Fig. 1aFigure 1), while its distribution is more homogeneous in COS-7 cells (Fig. 1cFigure 1). Interestingly, when both cell lines were transiently transfected with Atx3 N-terminally tagged with GFP (GFP-Atx3 (28Q), Figs. 1e and 1gFigure 1), Atx3 was found predominantly in the cytoplasm of both cell types, in agreement with previous data [5], [6], [45].
Figure 1
Figure 1

Figure 1
Ataxin-3 can shuttle between the nucleus and the cytoplasm.
In order to determine whether Atx3 can be actively transported across the nuclear membrane we analyzed the effect of leptomycin B, a specific covalent inhibitor of the nuclear export factor CRM1/exportin [46], [47], on the subcellular distribution of both endogenous and overexpressed Atx3 in HEK293 and COS-7 cell lines. In eukaryotic cells, nuclear export of proteins is frequently mediated by this nuclear export factor, which binds to nuclear export signals (NES) on cargo molecules. If Atx3 is a nuclear shuttling protein, interfering with its putative nuclear export would be expected to modify Atx3 subcellular localization by increasing the proportion of the protein localized in the nucleus. Indeed, after cell treatment with leptomycin B both endogenous Atx3 (Figs. 1b and fFigure 1) and transfected GFP-Atx3 (28Q) (Figs. 1d, hFigure 1) accumulate in the nucleus of a subpopulation of cells, suggesting that Atx3 exits the cell nucleus by active transport at least partially dependent on the CRM1/exportin pathway. In COS-7 cells the nuclear accumulation of GFP-Atx3(28Q) could be observed in 26.5±4.5% of cells after leptomycin B treatment, whereas in untreated cells only 4.8±2.4% of cells showed nuclear accumulation of the protein. Nuclear export dependent on CRM1 receptor has also been demonstrated for other proteins containing expandable polyglutamine tracts such as ataxin-7 [32] and huntingtin [33]. In agreement with what is observed for Atx3 in the context of the full-length protein, leptomycin B treatment of cultured cells tranfected with huntingtin lead to a partial nuclear accumulation of the protein corresponding to a 10% increase in nuclear fluorescence of huntingtin [33].
Ataxin-3 contains a functional nuclear localization signal
Translocation of macromolecules larger than 40–60 kDa in and out of the nucleus is an active, energy-dependent process that is mediated by specific sequence motifs: nuclear localization signals (NLS) and nuclear export signals (NES). “Classical” examples of NLSs are the highly basic motifs originally found in the simian virus 40 (SV40) large T antigen and in nucleoplasmin, although several sequences differing from those basic ones have also been shown to function as NLS [48], [49], [50]. In “classical” nuclear import, importin-α recognizes and binds the target proteins in the cytoplasm, mediating their transport across the nuclear pore complex after formation of a ternary complex with importin-β [48], although some NLS-containing cargoes can be directly recognized by importin-β without the need of the adaptor protein. Within importin-α, the major NLS binding pocket contains a series of negatively charged residues that form salt bridges with the basic residues within the NLS sequences [51]. A putative NLS has been identified within the amino acid sequence of Atx3 [5], which is conserved among Atx3 proteins from diverse species (Fig. 2Figure 2).
Figure 2
Figure 2

Figure 2
Human ataxin-3 and its closest homologues contain conserved nuclear import sequences.
In order to test the functionality of the identified NLS sequence, we used a pNIA vector-based genetic one-hybrid system that allows identification of nuclear proteins in yeast cells [39]. This assay is based on the functional outcome of the nuclear import of the tested protein, which, if it reaches the yeast cell nucleus, allows specific induction of a reporter gene. The advantage of this approach is allowing the quantitative evaluation of the strength of the nucleocytoplasmic shuttling signals, independently of the cellular model. This system has been consistently used for mutational analysis of nuclear proteins to delineate and characterize the NLS [52] and for testing the integrity of the nuclear pore complex permeability barrier [53]. The rationale for this assay is the expression in the yeast S. cerevisiae cells of the test protein fused to a modified LexA DNA binding domain (DBD) and the Gal4 transcriptional activation domain (AD). This transcription based assay relies on the ability of a functional NLS to allow the chimera to enter the yeast nucleus and activate transcription of a LexA responsive β-galactosidase or HIS3 reporter gene. In the absence of a functional NLS, the fusion protein is not efficiently imported into the nucleus, and is unable to activate transcription. As a result, this assay provides a simple measure of NLS function based either on the quantitative determination of β-galactosidase activity or on the qualitative analysis of yeast growth in a medium lacking histidine. This system is not limited to the identification of yeast NLSs, as the nuclear import apparatus is highly conserved between yeast and higher eukaryotic cells [49], [50].
pNIA-GFP and pNIA-SV40NLS were used as controls for the nuclear import assay. pNIA-GFP encodes the fusion protein mLexA-Gal4AD-GFP and was used as negative control because it is not imported into the nucleus, resulting in minimal expression of the two reporter genes, whereas pNIA-SV40NLS encodes the fusion protein mLexA-SV40NLS-Gal4AD-GFP which, due to the presence of the SV40NLS, is actively imported into the nucleus, leading to high activity of both lacZ and HIS3 genes. The cDNA for ataxin-3 (with 28 glutamines) was cloned in the pNIA vector, and to ensure that the resulting fusion protein had a molecular weight not compatible with simple diffusion across the nuclear pore, GFP was inserted between Gal4AD and Atx3. When expressed in yeast, the pNIA-GFP-Atx3 fusion protein induced growth on histidine-deficient medium (data not shown), suggesting that Atx3 was actively imported into the nucleus. To confirm this result we performed a quantitative β-galactosidase assay, in liquid culture of yeast cells expressing the different constructs (Fig. 3Figure 3). The results obtained show that pNIA-GFPAtx3 induced levels of β-galactosidase activity significantly higher than the levels obtained for pNIA-GFP, a finding which confirms that Atx3 is actively imported into the nucleus of yeast cells.
Figure 3
Figure 3

Figure 3
Evaluation of the nuclear import capacity of ataxin-3 protein in yeast.
To determine whether the proposed NLS of Atx3 was indeed responsible for the translocation of the fusion protein into the nucleus of yeast cells, we mutated the conserved arginine residue within the putative NLS sequence into a threonine residue (pNIA-GFP-Atx3R282T). This mutation is a typical mutation performed in the analysis of conserved NLS sequences since it changes a basic residue for a neutral residue without modifying its polar character [28], and has also been shown to disrupt the function of the NLS identified in ataxin-1 and ataxin-7 [28], [30]. As shown in Figure 3Figure 3, the mutation results in the reduction the β-galactosidase activity to levels similar to the negative control (pNIA-GFP), indicating that the mutation greatly impairs Atx3 nuclear import in yeast. The mutation of the same arginine residue to an alanine residue (pNIA-GFP-Atx3R282A) was also tested, and resulted in a reduction on the nuclear accumulation of the fusion protein (Fig. 3Figure 3). These data show that interference with the putative NLS disrupts the nuclear import ability of Atx3.
The nuclear import activity of Atx3 was further confirmed in mammalian cells by comparing the subcellular localization of GFP-Atx3(28Q)R282T with GFP-Atx3(28Q) (Fig. 4Figure 4). When transfected in COS-7 cells, both constructs localized mainly in the cytoplasm of the cells. Because our data show that Atx3 can also be exported from the nucleus and that this export is at least partially mediated by the CRM1 pathway (see above), the similar localization of wild-type Atx3 and the R282T mutant might be due to the presence of competitive nuclear export signals. Therefore, in order to investigate if there is a difference between the nuclear shuttling ability of the wild-type protein and the R232T mutant in COS-7 cells, we incubated the cells with leptomycin B, thereby at least partially inhibiting nuclear export, and determined their subcellular re-localization. As shown in Fig. 1Figure 1 (panels g and h), GFP-Atx3(28Q) accumulates in the nucleus of a subpopulation of cells in the presence of leptomycin B. When GFP-Atx3(28Q)R282T is expressed in COS-7 cells this nuclear accumulation is not observed (Fig. 4Figure 4), indicating that the identified NLS sequence is also responsible for driving Atx3 into the nucleus of mammalian cells. Therefore, we conclude that Atx3 contains a basic NLS sequence that is functional and promotes its active import into the cell nucleus.
Figure 4
Figure 4

Figure 4
Evaluation of the nuclear import ability of ataxin-3 in mammalian cells.
The nuclear export of ataxin-3 is mediated by CRM1-dependent and -independent pathways
Since the nuclear export of Atx3 was partially inhibited in the presence of leptomycin B (Figs. 1Figure 1, ,4),4Figure 4), we analyzed the nuclear export activity of Atx3 using the Rev(1.4)-GFP nuclear export assay [42]. This assay is based on the expression of fusion proteins consisting of Rev(1.4), an export-defective HIV-1 Rev protein mutant, the sequence to be tested, and GFP. The nuclear export functionality of the sequence to be tested is evaluated by analyzing its capacity to promote nuclear export of the Rev(1.4)-GFP fusion protein. The Rev(1.4)-GFP fusion protein, which was used as a negative control for this assay, was localized exclusively in the nucleus of COS-7 cells, presenting a clear nucleolar accumulation (Fig. 5bFigure 5). Rev(1.4)-NES–GFP, a fusion protein that contains the Rev NES, which was used as a positive control for this assay, was localized in the nucleus and the cytoplasm of transfected cells (Fig. 5bFigure 5). The number of cells presenting exclusively cytoplasmic localization was enhanced following actinomycin D (ActD) treatment (Fig. 5bFigure 5), which blocks the nuclear import mediated by the Rev NLS [42], whereas the cytoplasmic localization of Rev(1.4)-NES-GFP was completely blocked by addition of leptomycin B (Fig. 5bFigure 5), as expected for a protein whose nuclear export is dependent on CRM1.
Figure 5
Figure 5

Figure 5
The nuclear export of ataxin-3 is mediated by the protein N-terminal domain.
Full-length Atx3 containing 28 glutamine residues [Atx3(28Q)], when fused to Rev(1.4)-GFP, was driven into the nucleus, where it formed punctuate structures resembling the insoluble nuclear inclusions (Fig. 5bFigure 5). The morphology of these structures is clearly distinct from the nucleolar accumulation of fluorescence observed for Rev(1.4)-GFP (Fig. 5bFigure 5). We also tested full-length Atx3 containing 84 glutamine residues [Atx3(84Q), Fig. 5bFigure 5], which formed punctuate structures, presumably aggregates, in the nucleus of transfected cells. These structures were not sensitive to the blockade of nuclear import of the Rev fusion protein using ActD. In fact, this result is in agreement with previous observations that Atx3 has a tendency to oligomerize independently of the expanded polyQ tract [54], [55], [56] and that the nuclear environment promotes protein misfolding and aggregation [57]. Curiously, it was observed that overexpression of ataxin-7 in cell culture models induced the nuclear localization of the protein and formation of large protein “accumulations” in ~30% of the cells, independently of the polyglutamine tract size [30].
The nuclear aggregation of full-length Atx3 when fused to Rev(1.4)-GFP, independently of the extent of the polyQ tract, presumably triggered by the strong Rev NLS, hampered the investigation of the nuclear export activity of full-length Atx3 using this system. Therefore, we prepared constructs encoding various domains of Atx3 fused to Rev(1.4)-GFP, all lacking the polyglutamine tract and the endogenous NLS (Fig. 5aFigure 5). The fusion protein consisting of the Josephin domain of Atx3 [JD-(1–182)] fused to Rev(1.4)-GFP showed a distribution between the cell nucleus and cytoplasm in 46% of the cells after cell treatment with ActD (Fig. 5bFigure 5). We also tested the cellular localization of the fusion protein consisting of the Josephin domain followed by the segment of Atx3 that contains the UIMs [Atx3(1–263)], fused to Rev(1.4)-GFP [Rev1.4-Atx3(1–263)-GFP]. This protein also displayed a nuclear and cytoplasmic localization, and the number of cells showing a mixed distribution of the protein increased to 78% after cell treatment with ActD (Fig. 5bFigure 5). The nuclear export activities of JD(1–182) and Atx3(1–263) were not inhibited by the CRM1 export inhibitor leptomycin B (+LMB).
These results suggest that the Josephin domain can mediate the nuclear export of the fusion proteins, which requires the context of the Josephin domain plus a sequence downstream this catalytic region. However, this UIM-containing segment alone [Rev(1.4)-Atx3(183–263)-GFP, Fig. 5bFigure 5] was not sufficient to promote nuclear export of the fusion protein. Finally, we asked whether the nuclear export of the Atx3(1–263) fragment was dependent on the ubiquitin binding capacity of its UIMs. It has been shown, in a cell-based assay of polyQ aggregation, that recruitment of non-expanded Atx3 into nuclear aggregates is mediated by its UIMs [58]. Therefore, we mutated the two UIMs in the Atx3(1–263) fragment in order to compromise their functionality [Atx3(1–263)(S236A,S256A)]. This protein had the same pattern of cellular distribution as the wild-type Atx3(1–263) fragment (Fig. 5bFigure 5), indicating that functionality of the UIMs is not required for the increased nuclear export activity observed for this region of Atx3.
Our results clearly demonstrate that nuclear export of Atx3 is dependent on a complex Atx3 motif, located in the N-terminal portion of the protein, which requires the context of the Josephin domain plus the ubiquitin-interacting motifs. Taken together, these data indicate either that nuclear export of Atx3 is mediated by a nuclear export receptor that recognizes a properly folded conformational motif and/or that multiple export pathways contribute to the overall nuclear export of full-length Atx3. Interestingly, a nuclear export receptor, exportin 7, has been recently described, which recognizes nuclear export signals that include conformation-dependent recognition motifs, rather than short linear sequences [59].
Since we observed nuclear accumulation of Atx3 in a population of COS-7 cells when the CRM1 transporter was inhibited with leptomycin B (Figs. 1Figure 1 and and4),4Figure 4), we looked for leucine-rich nuclear export signal (NES) sequences within Atx3 primary structure that might match the consensus NES sequence for the CRM1-dependent export [60], using the NetNES predictor (http://www.cbs.dtu.dk/databases/NESbase-1.0 [43]). We found 6 putative NES sequences, of which 4 are present within the Josephin domain (Fig. 2Figure 2, NES1-NES4), one is located between the Josephin domain and the first ubiquitin interaction domain (NES5) and the last one (NES6) corresponds to the first ubiquitin interaction motif of the protein (Fig. 2Figure 2). We have fused the putative NESs identified in Atx3 with Rev(1.4)-GFP, and tested whether the presence of these sequences can induce the translocation of Rev(1.4)-GFP from the cell nucleus. However, the isolated NES sequences failed to induce nuclear export when inserted into the Rev(1.4)-GFP vector (Table 1). The observation that in this system none of the tested sequences showed nuclear export activity can result from the fact that these sequences do not function as active leucine-rich nuclear export signals, but could also be a consequence of testing the sequences isolated from their overall protein context. For example, the isolated NES of Rev binds to CRM1 much more weakly than does the full-length Rev protein [61], implying that an NES may require flanking sequences to adopt the conformation needed for CRM1 binding. Another possibility is that each isolated sequence is not strong enough to drive detectable nuclear export of Rev1.4-GFP, which has a very strong NLS, and that several NESs work in concert to achieve efficient export of Atx3. In fact, recent studies show that most NESs bind to CRM1 with relatively low affinity, since high-affinity NES binding to CRM1 impairs the efficient release of export complexes from the nuclear pore complex [60].
Table 1

Table 1
Analysis of the nuclear export activity of putative NES sequences within ataxin-3 primary structure.
The nuclear export of GFP-Atx3(28Q) was partially inhibited by leptomycin B (Figs. 1Figure 1, ,4),4Figure 4), suggesting that a CRM1-dependent pathway is involved in the nuclear export of Atx3. On the other hand, using the Rev(1.4)-GFP fusion system, which contains a strong NLS, we detected nuclear export activity of the N-terminal portion of Atx3 (Josephin domain and UIMs) that was not sensitive to leptomycin B (Fig. 5bFigure 5). This supports the possibility that, in resemblance to what has been found for huntingtin [33], [34], CRM1-dependent and -independent nuclear export mechanisms coexist to cooperate in determining the subcellular distribution of Atx3. In the context of the full-length protein, one of these pathways may be dominant when compared to the other. Similar to that of Atx3 and huntingtin, the nuclear export of other proteins, such as α-catenin [62], receptor-interacting protein 3 (RIP3) [63] and the African Swine Fever Virus p37 protein [64], has been shown to be mediated by both CRM1-dependent and –independent pathways.
Conclusion
A correlation between the nuclear environment and protein aggregation in MJD models has been pinpointed by studies using Atx3 with an exogenously added NLS that demonstrated in situ that the nuclear environment drives aggregation of both expanded and non-expanded Atx3 [57], [65]. Recent in vivo studies have shown that adding an exogenous NES does not only suppress the formation of NIIs almost completely, but also seems to prevent the aggregation of Atx3 [35]. Furthermore, live-cell imaging studies showed that expanded polyQ tracts slow the dynamics of intact Atx3, and that the export of expanded Atx3 is less efficient than the export of normal Atx3 [66], suggesting a defect on the nucleocytoplasmic shuttling activity of the expanded protein. In fact, a recent study using a Drosophila system to screen for genetic modifiers of Atx3 neurodegeneration identified as a suppressor of Atx3-mediated toxicity, among others, the gene encoding the nuclear export protein Embargoed, the orthologue of human CRM1 [67]. In order to further understand the link between nuclear localization, aggregation and toxicity of expanded Atx3, it is essential to identify the mechanisms behind the intracellular dynamics of the normal protein. In this study, we have confirmed the functionality of the putative Atx3 NLS in yeast and mammalian cells, and detected CRM1-dependent and –independent pathways that mediate the nuclear export of Atx3. Our data show that the CRM1-independent nuclear export of Atx3 is mediated by the N-terminal region of the protein and is critically dependent on a three-dimensional motif whose integrity is compromised when the Josephin domain is physically separated from the UIMs. Future identification of the nuclear transporter(s) responsible for this pathway, will pave the way to determining how the subcellular localization of Atx3 is regulated in physiological or pathological conditions.

Acknowledgments
We are grateful to Henry Paulson for providing the pEGFP-C1-ataxin-3(28Q) plasmid, as well as the anti-ataxin-3 antibody, to Vitaly Citovsky for providing the pNIA vector and the Saccharomyces cerevisiae L40 strain, and to Beric R. Henderson for providing the Rev(1.4)-GFP and the Rev(1.4)-NES-GFP plasmids. We thank Ana Eulálio and Maria C. Pedroso de Lima for helpful advice and discussions.

Footnotes
Competing Interests: The authors have declared that no competing interests exist.
Funding: This work was supported by a grant from the Portuguese Foundation for Science and Technology (POCI/SAU-MMO/60156/2004) and by Crioestaminal/Associacao Viver a Ciencia. LC was a recipient of a post-doctoral fellowship from the Portuguese Foundation for Science and Technology (SFRH/BPD/20686/2004/22). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Top
Abstract
Introduction
Methods
Results and Discussion
References

References
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Cure PSP Webinars

2009-09-29T18:16:00.000-07:00

Richard recently received an email to participate in a series of webinars sponsored by Cure PSP. He attended and enjoyed Dr. Susan Perlman's webinar "Ataxia, OPCA & MSA-C Look-A-Likes of PSP, CBD & MSA" on September 17, 2009. Here is the link to the slides of her presentation.

There are a series of webinars that are available in the next few months. In case anyone is interested, I am duplicating the email invitation to participate:

Please immediately respond to this advance invitation to ensure yourself a seat at the Movement Disorder Specialists’ FREE Webinar series sponsored by CurePSP.

Dr. Neal Hermanowicz, October 8, 2009

Dr. Robert Hutchman, October 22, 2009

Dr. Yvette Bordelon, November 5, 2009

Dr. Lawrence Golbe, November 19, 2009

Dr. Jerome Lisk, December 3, 2009

As a friend of the CurePSP you are offered a special priority to register for this Webinar.

There is only a maximum of 1,000 seats (144 seats gone in the first few days) available for each of these Webinars. We suggest that you register early, as the limited number of world-wide seats will go very, very fast. Attending the last Webinar by Dan Brooks were people from not only the United States and Canada, but also from Great Britain, France, Andorra, Kuwait, Taiwan and Australia.

Reserve your Webinar seat RIGHT NOW by CTRL left clicking on the above red button to register or copying and pasting the below link into your Web Browser:

https://www2.gotomeeting.com/register/747740042

DR. NEAL HERMANOWICZ attended Temple University for medical school. He completed a general medicine internship and residency in neurology at the University of Wisconsin and his Movement Disorders Fellowship with Drs. Anne Young and Jack Penney at the University of Michigan from 1989 to 1991. He is a fulltime faculty in the Department of Neurology at the University of California, Irvine where he is Health Sciences Professor of Neurology and has served as the director of the Movement Disorders Program since 1999. Dr. Hermanowicz also serves as the director for the Phillip & Carol Traub Center for Parkinson’s Disease of the Eisenhower Medical Center in Rancho Mirage, CA, a position he has held for 10 years. Dr. Hermanowicz is a clinician and is engaged foremost in patient care, but also clinical trials and research in the area of Movement Disorders.

Dr. Robert Hutchman completed his Movement Disorder Fellowship at the Mayo Clinic, Rochester, MN in 2002. His undergraduate medical training was completed at the Wayne State University School of Medicine in Detroit, MI. Since completing his training he has served as Sub-Investigator on approximately ten (10) Phase 2 thru 4 clinical drug trials. Following that incredible opportunity to develop clinical research and deep brain stimulation surgery management skills, Dr. Hutchman entered private practice in Southern California. Since arriving in California, he has founded a private practice exclusively serving a unique patient population composed of neurodegenerative disorders. As the founder and Medical Director of Neurosearch, Dr. Hutchman has successfully administered ten (10) additional clinical trials.

Dr. YVETTE BORDELON received her MD and PhD degrees from the University of Pennsylvania. Her thesis work was performed with Dr. Marie-Francoise Chesselet and involved investigating mechanisms of cell death in an animal model of Huntington disease. She went on to residency training at Massachusetts General and Brigham and Women’s Hospitals and then did a Movement Disorders Fellowship at Columbia University before joining the Neurology faculty at UCLA in 2004. Her clinical work involves the diagnosis and treatment of Movement Disorders and her clinical research interests include clinical trials and development of biomarkers of disease in this subspecialty.

DR. LAWRENCE I. GOLBE, (world renowned expert in PSP and CBD), a Movement Disorder Specialist and Professor of Neurology, Robert Wood Johnson School of Medicine, New Brunswick, New Jersey. He is on the CurePSP+ Board of Directors and the Chair of the CurePSP+ Scientific Advisory Board (SAB).

Dr. Jerome P. Lisk is a fellowship trained Movement Disorder Neurologist. He completed his fellowship at the University of Texas at Houston. He specializes in the treatment of Parkinson’s Disease, Parkinson’s Plus Syndromes, Cervical Dystonia and other movement disorders. Dr. Lisk earned his medical degree at the Medical College of Virginia in Richmond, Virginia. Dr. Lisk is Board Certified by The American Board of Psychiatry and Neurology. He also has an interest in dementia and sleep disorders. Dr. Lisk is on the staff at Huntington Memorial Hospital, Aurora Las Encinas Hospital, Casa Colina Hospital, Methodist Hospital and City of Hope Cancer Center all in Southern California.

Reserve your Webinar seat RIGHT NOW by CTRL left clicking on the above red button to register or copying and pasting the below link into your Web Browser:

https://www2.gotomeeting.com/register/747740042

TITLE OF OCTOBER 8, 2009 PRESENTATION
“Fundamentals & Diagnosis of PSP, CBD, MSA and Related Brain Disorders”
Dr. Neal Hermanowicz

TITLE OF OCTOBER 22, 2009 PRESENTATION
“Interventions in PSP, CBD, MSA and Related Brain Disorders”
Dr. Robert Hutchman

TITLE OF NOVEMBER 5, 2009 PRESENTATION
“Latest Research in PSP, CBD, MSA and Related Brain Disorders”
Dr. Yvette Bordelon

TITLE OF NOVEMBER 19, 2009 PRESENTATION
“PSP, CBD, MSA and Related Brain Disorders Research for Dummies”
Dr. Lawrence Golbe

TITLE OF DECEMBER 3, 2009 PRESENTATION
“Two (2) hours of Medical Questions & Answers about PSP, CBD, MSA and Related Brain Disorders”

Dr. Jerome Lisk

TIME
8:00 PM Eastern Time
7:00 PM Central Time
6:00 PM Mountain Time
5:00 PM Pacific Time

Daylight Savings Time in the United States reverts to Standard Time on the first Sunday in November, so times outside of the United States might change for the November and December Webinars.

1:00 AM United Kingdom/London Time (following day)
2:00 AM South Africa/Johannesburg Time (following day)
10:00 AM Australia/Sydney Time (following day)

DURATION
10 minute introduction
40 minute presentation
10 minute refreshment/toilet break
60 minutes of Questions and Answers

Patients, caregivers, family members and medical and healthcare professionals from across the United States and Canada and from most countries of the world can listen and/or view these live Webinar. The presentation will provide guidelines to the diagnosis, treatments and research of Parkinsonism, also known as the Parkinson’s Plus Syndromes or Atypical Parkinsonian Disorders.

The upcoming Webinars are sponsored by CurePSP (Foundation for PSP | CBD and Related Brain Diseases).

You may listen and view each of the Webinars (via a slide show presentation) from the convenience of your home or office, using your computer and your attached speakers. This is FREE! No special computer software is necessary.

Or you may listen only to each of the Webinars using your land or mobile telephone. Line charges are your responsibility.

Reserve your Webinar seat RIGHT NOW by CTRL left clicking on the above red button to register or copying and pasting the below link into your Web Browser:

https://www2.gotomeeting.com/register/747740042

How to address questions to the presenters:

v During the registration process you can ask one or more questions in the “Questions & Comments” box at the end of the registration form.

v Once you have registered for these Webinars you can, up to one (1) day prior to the start of each of the Webinars, e-mail the presenter a question at Webinar.Question@gmail.com .

v If you are listening and viewing the Webinar via your computer, you can submit your questions online via the Webinar's Instant Messaging (IM) service.

v If you are listening to the Webinar via your telephone, you will not be able to ask your questions.

If you have any questions, please contact the Webinar Organizer, Outreach & Education Committee, CurePSP+ at CurePSP.Webinar.Coordinator@gmail.com .

*A Webinar is a FREE computer based web conference with up to 1,000 people from around the world viewing the conference. It is typically one-way, from the presenter to the audience. The presenter speaks to the audience, using a computer attached microphone. He/she points out information being presented via the mouse pointer on the viewers home or office computer screen. It is also possible to just listen to the presentation via a land or mobile telephone. The cost of the telephone call is paid for by the listener.
Larry Schenker

Atypical Parkinsonian Disorders Support Groups
Southern California – Mexican border north to Santa Barbara & Kern Counties
Organizer & Co-Leader
================================================================
CurePSP+ (Foundation for PSP + CBD + Related Disorders)
Outreach and Education Committee Member
Webinar Organizer
Online Support Group Organizer
================================================================
Los Angeles, California, United States of America
Tel: (310) 441-1488 - E-mail: atypical.parkinsonian.disorder@gmail.com

If you want someone to be added to this meeting notice list, send an e-mail giving the person’s name and e-mail address to subscribe.ATP@gmail.com

Taltirelin

2009-09-28T23:44:00.000-07:00

A little while ago, a member on the MJD Family forum posted about a drug called Ceredist (generic name: Taltirelin) that is only available by prescription in Japan. Her mother, who is Japanese, has taken the drug for a few years. Ceredist is manufactured by a Japanese pharmaceutical company, Mitsubishi Tanabe Pharma.

Wikipedia's entry on Taltirelin reads:

Taltirelin (marketed under the tradename Ceredist) is a thyrotropin-releasing hormone (TRH) analog, which mimics the physiological actions of TRH, but with a much longer half-life and duration of effects,^[1] and little development of tolerance following prolonged dosing.^[2] It has nootropic,^[3] neuroprotective^[4] and analgesic effects,^[5] and is primarily being researched for the treatment of Spinocerebellar ataxia.

The member who made this post was uncertain whether or not the drug had any beneficial effects on her mother but hypothesized that "it has slowed down the disease, if anything."

It might be something that an MJDer who is living Japan might consider following up on but has probably been made aware of by the physicians there already. In any case, it is reassuring to know that there is at least one pharmaceutical company that has successfully developed and marketed a drug (albeit perhaps on the palliative side) for SCA.

Voice of dissent

2009-09-27T13:48:00.000-07:00

It has been a while since our last post. Life has lapsed into a lulling routine of Pilates classes, PT sessions and work-outs at the Y. Richard continues to make progress in his PT sessions and his stamina remains good. He has taken up Sudoku puzzles to keep his mind sharp. At the rate he's going, I won't be surprised if he achieves "grand master" standing soon!

On a different note, this past April I received an email from Fabio, the son of Nadia, a fellow Nanshan patient who passed away in June 2008 from ALS. In his email to us, Fabio asked us to read his post dated April 22, 2009 which contained an RAI (Italian TV) program that had subsequently been posted in five installments on youtube for public viewing.

It is my understanding that Fabio and Nadia worked with Beike Europe, the European branch of Beike Biotechnology in China, for their trip to China for stem cell therapy in March 2007. Fabio is among the many Italians who were dissatisfied with the lack of results and response from Beike after their trip to China. Their frustration culminated in a confrontation with a Beike Europe official on the TV program.

Since I neither speak nor read Italian, I had to get my friend, Arianna, who is Italian, to translate the program for me. Here's her synopsis:

The head of Beike Europe (who does not have a science background, he has a marketing background) is trying to defend himself from angry customers that did not obtain a result. There is a scientist who says that the problem with Beike is that it has not one clinical study published on the treatments, pre- and post comparisons, there is no data on effectiveness nor on follow-up. Another doctor (the elderly looking one) puts Beike to shame by saying that it is unethical to promise such benefits when there is no data to support it.

In her article in Macleans.ca, "To China with a cure", Alexandra Shimo wrote:

Patients, like Haas, who seem to have been helped by stem cell treatments, are often eager to share their stories. They may become advocates for the Chinese medical centres; Haas’s story is publicized on the website of the company that organized his medical tourism trip. By contrast, it’s more difficult to find people who haven’t gotten better, or are worse after spending $30,000 on an experimental procedure. This might be because they feel duped, or because the Chinese stem cell treatment emphasizes empowerment—a “you can do it attitude.” Those who can’t “do it,” who go through the rigorous training program and end up no better off, may feel unlucky, cheated, or they may take the lack of success personally and feel that they have somehow failed.

I think Ms. Shimo can rest easy knowing that there are those few who will not rest until they find the truth. However, the price of being a truth seeker is a terrible one. Fabio appeared on the RAI program with his sister. He is the earnest young man in a dark suit and red tie. One does not have to understand Italian to be touched by the pain on his face when he was reminiscing about his mother and her illness. It is an image that will haunt me for a long time.

Update on the Chantix (Varenicline) trial

2009-05-28T14:37:00.000-07:00

Thank you to Mike Fernandes who has been keeping close tabs on the Chantix (Varenicline) trial this summer. Here's what Mike learned:

PROTOCOL SYNOPSIS STUDY TITLE

A Pilot, Randomized, Double-blind, Placebo-controlled Phase I Study to Determine the Safety and Tolerability of Varenicline (Chantix®) in Treating Spinocerebellar Ataxia Types 1,2,3,and 6

SPONSOR

National Ataxia Foundation; Bobby Allison Ataxia Research Center
(Sites: U of South Florida, U of Chicago, UCLA, Emory, U of Florida, U of Minnesota)

CLINICAL PHASE

2

STUDY RATIONALE

Spinocerebellar ataxia (SCA) is a group of inherited disorders characterized by cerebellar degeneration leading to imbalance, incoordination, speech difficulties and problems with walking.

Recently, individual case reports have suggested that Varenicline, a drug used in smoking cessation, produces substantial improvement in patients with several inherited ataxias.

A modest response was noted in 5 patients with SCA, suggesting that it is potentially efficacious in this disorder as well. Although this agent is available for off-label use, the severe side effects noted with its use and the lack of long-term toxicity data demand that it be systematically assessed. The present study will test whether Varenicline is safe and potentially efficacious in a heterogeneous cohort of adults with SCA.

STUDY OBJECTIVE(S)

The primary outcomes will be the changes in the patient’s SARA Rating Scale total score and frequency and severity of dose-limiting adverse events.

The secondary objectives of this study are to assess:

the effect of Varenicline on quality of life in patients with spinocerebellar ataxia

the effect of Varenicline on depression and anxiety ratings

the effect of Varenicline on the activity of daily living (ADL) in patients with spinocerebellar ataxia

TEST ARTICLE

Varenicline

STUDY DESIGN

This is a double-blind, parallel group, randomized, placebo-controlled, crossover pilot study

NUMBER OF SUBJECTS

40 subjects overall

6 sites

STUDY DURATION

175 days(± 3 days) per subject

Furthermore, according to Mike, this trial will not be recruiting for test subjects until this summer. Here are a few links that Mike provided to Dr. Theresa A. Zesiewicz of the University of South Florida who will be conducting the study and the study itself:

http://hsc. usf.edu/NR/ rdonlyres/ E1ABA07F- CA90-4B38- B507-E13BCA3FC29 D/0/ProtocolSynopsis.pdf

http://www.ataxia. org/research/ studies/2009/ naf-research- zesiewicz. aspx

http://health. usf.edu/medicine /neurology/ faculty/zesiewic z.htm

On a separate note, Dr. Perlman prescribed Chantix for Richard some time ago to see if it helped him. However, after taking the drug for two months, we did not note any discernible improvement. Therefore, Dr. Perlman decided to take it off Richard's meds list. She will append Richard's results to the study so that his stint and effort as guinea pig will not be wasted.

Hot off the presses from the NAF

2009-04-05T17:04:00.000-07:00

We received the following email from the National Ataxia Foundation (NAF):

2009 Annual Membership Meeting Presentations

The National Ataxia Foundation is pleased to announce that many of the power point presentations given at the 2009 NAF Annual Membership Meeting are now available on the Foundation's web site, www.ataxia.org.

The 52nd NAF Annual Membership Meeting, "Climb Every Mountain," was co-hosted by the Seattle Area Ataxia Support Group and the British Columbia Ataxia Society. The meeting was held on March 20 - 22, 2009 and people from around the United States and attendees as far away as Australia and Hong Kong attended the meeting.

On Thursday, March 19, 2009 seventy cyclists from Ride Ataxia III arrived at the NAF Annual Membership Meeting. They began their journey four days earlier in Portland, Oregon and rode their bikes through rain and cold to help raise ataxia awareness and funds to support important ataxia research.

Friday, March 20, 2009 began with General Session speakers in the morning and "Birds of a Feather" sessions in the afternoon, followed by a Friday night reception. Saturday General Sessions continued throughout the day and ended with the traditional Saturday night banquet. Sunday continued with General Session speakers and concluded in the early afternoon.

The National Ataxia Foundation wishes to extend a heartfelt thank you to the Seattle Area Ataxia Support Group and the British Colombia Ataxia Society, all the knowledgeable speakers and presenters, our wonderful volunteers, our generous donors and sponsors, exhibitors, the Doubletree Hotel, the City of SeaTac, and especially all who registered to attend this important meeting. Thank you!

More information about the 2009 NAF Annual Membership Meeting will be available shortly on NAF's web site and in future issues of NAF's quarterly news publication, "Generations."

2010 Annual Membership Meeting

Start making your plans for next year's meeting. The 2010 NAF Annual Membership Meeting will be held in Chicago, Illinois on March 12 - 14, 2010 at the Hyatt Regency O'Hare. More information about the meeting will be available on NAF's web site, www.ataxia.org and in future issues of "Generations." See you in Chicago!

Here's a direct link to the power point presentations from the 2009 Annual Membership Meeting:

http://www.ataxia.org/events/2009-amm-presentations.aspx

An update on JC, a fellow Nanshan MJDer

2009-04-05T16:40:00.000-07:00

We recently came across an article in Macleans, a Canadian magazine, about Jean Christophe (JC) Haas. JC went to Nanshan Hospital in 2007, shortly after we left the facilities, to undergo stem cell treatment. We have corresponded with JC through email several times. JC and his wife, Cherie, has gone back to China since his initial treatment to get more stem cell injections. We have listed his blog on this website under "MJDers Blog about their stem cell therapy".

To China for a cure
by Alexandra Shimo
March 9, 2009
Macleans.ca

China is not normally considered a world leader in surgical advances, but according to a number of its doctors (and the Canadian patients they’ve treated), it has leapfrogged ahead in stem cell treatments. A growing number of people are travelling to China for a $30,000 experimental treatment: stem cell injections. Most, like New Brunswicker Jean Christophe Haas, 40, decide to go because they have a debilitating illness and there isn’t much that Western medicine can do for them.

Haas has Machado-Joseph disease (MJD), a terminal neuromuscular disease that affects the body in a similar way to Parkinson’s, paralyzing it gradually. Although he was diagnosed 20 years ago, it took some years for the symptoms to become noticeable. At first, only his sense of balance and his coordination were affected. Then his speech began to suffer and he started slurring his words. In 2004, he had to stop work as an army mechanic because his motor skills were no longer up to par and, in the past couple of years, he started seeing double. His family felt an overwhelming sense of panic, especially because Haas’s mother had the same disease, and his grandmother died of it. His desperation was compounded by the sense that Canadian doctors had given up on him completely; one told him there was nothing to do but to accept his fate of an early death, says his wife, Cherie Haas. “It’s awful for a young man with a family to go in and hear that. It’s heartbreaking.”

Ms. Haas searched the Web and found stories of other MJD patients who seemed to have been helped by stem cell therapy at various Chinese hospitals. Many of these good news stories are posted on personal blogs or on the websites of the clinics offering the treatments. There are thousands of these testimonials, suggesting that hundreds of people go every year, says Timothy Caulfield, Canada Research Chair in Health Law and Policy at the University of Alberta, who has published studies on this issue.

Advertising on the Internet, these Chinese medical centres promise to treat a surprisingly extensive range of diseases and conditions, including ALS, autism, brain injuries, cerebral palsy, epilepsy, multiple sclerosis, Parkinson’s, spinal muscular atrophy, septo-optic dysplasia (which can cause seeing difficulties, blindness and mental retardation), spinal cord injuries and stroke. Foreigners are a major source of funds for the clinics. Some doctors like Dr. Huang Hongyun, a neuroscientist at Beijing Xishan Hospital, have treated many patients from outside China, including some from Canada, and he has published a number of papers in Chinese medical journals tracking patients pre- and post-procedure. And yet some North American doctors are critical of how the data was compiled, and skeptical of the treatments on offer.

Once Jean Haas decided to go, he told his plans to Guy Rouleau, a neurologist at Centre Hospitalier de l’Université de Montréal, who said there were slight risks of complications, and that it would probably be a waste of money. But otherwise he didn’t try to dissuade him. Raising the money for the trip was easier than expected: much of the town of Oromocto, N.B., pitched in to raise the $30,000, with neighbours’ kids shovelling driveways to help out, and the military and community organizations hosting breakfasts and fundraisers. In April 2007, he and his wife travelled to Shenzhen, China, and stayed a little more than a month. During that time, Haas had six injections of stem cells into his spine, and an intense program of physiotherapy, exercise, massage and acupuncture. The results were immediate, he says—his balance improved just a few hours after the first procedure. Back in Canada, his neurologist confirmed that Haas had indeed gotten better: he had about 10 to 15 per cent more movement, according to Rouleau, who examined him before and after the trip. It’s difficult to speculate why this occurred, but Rouleau believes the intense physiotherapy was the primary cause.

When the couple returned from China, they wrote about their experience on the Web. Word got around, and soon hundreds of people were calling them, Cherie says. A couple whose husband had a similar neurodegenerative disease even drove from Quebec to see them, and the man subsequently decided to make the stem cell trip. Another couple flew in from Taber, Alta., and decided to go to China after seeing the home videos of Haas’s progress. Those gains were partly due to the attitude of Chinese doctors, Cherie believes. They would tell Haas to push himself to his limit and even try to “retrain his brain,” she explains. “We saw miracles while we were over there. We put the word out because I know this works.”

Even if patients experience gains, it’s important to determine whether they are from the treatment, the exercise program or a more positive frame of mind. Any advances could be merely the placebo effect, as people often feel better after being treated, even if the procedure hasn’t worked and the gains won’t last, explains John Steeves, a professor at the college for interdisciplinary studies at the University of British Columbia who specializes in spinal cord injuries. Finding out whether any treatment really works requires clinical trials, and although Dr. Huang has published the results of his trials in Chinese medical journals, this data does not conform to international standards of medical analysis. Indeed, Steeves believes Huang deliberately flouts these standards to help his bottom line. “Dr. Huang has no interest doing a valid clinical trial because if it doesn’t give him good results, his income would dry up immediately,” he says from his Vancouver office.

Patients, like Haas, who seem to have been helped by stem cell treatments, are often eager to share their stories. They may become advocates for the Chinese medical centres; Haas’s story is publicized on the website of the company that organized his medical tourism trip. By contrast, it’s more difficult to find people who haven’t gotten better, or are worse after spending $30,000 on an experimental procedure. This might be because they feel duped, or because the Chinese stem cell treatment emphasizes empowerment—a “you can do it attitude.” Those who can’t “do it,” who go through the rigorous training program and end up no better off, may feel unlucky, cheated, or they may take the lack of success personally and feel that they have somehow failed.

Missouri resident Jeff Carneal, 38, doesn’t feel like a failure, but having spent so much money, he is frustrated and disappointed. He lost the use of his legs when he fell off a stepladder while fixing his father’s barn. He has spent the past six years working with different doctors trying to learn to walk again, even flying to Quito, Ecuador, for an experimental operation (nerves were removed from his legs and grafted onto his spinal cord, which cost a lot, but didn’t really help). When a Maclean’s reporter first met Carneal at the Beijing Xishan Hospital after stem cell treatment, he was enthusiastic and believed the operation he’d had a couple of weeks earlier had alleviated some of the shearing leg pain he’d felt ever since his accident. But when contacted a few weeks after he returned to the United States, he was more downbeat, and said the operation hadn’t really made any difference.

Negative outcomes aren’t widely reported, but they are more common than the Chinese hospitals would have you think, says James Guest, a professor of neurological surgery at the University of Miami. He visited Huang in Beijing in the summer of 2004 to sample and test the fluid being injected into foreign patients. The results were inconclusive, he says. Following this, he went a step further, and examined spinal cord injury patients pre- and post-treatment in China. The results, published in 2006 in the journal Neurorehabilitation and Neural Repair, make clear the difference between what the doctors see and what patients want to believe. Of the seven, six thought they recovered some limb movement, although in most cases the physicians measured very little difference.

A few had concrete gains: a 19-year-old had chronic, burning back pain that eased enough for the patient to stop taking painkillers. Another patient had fewer muscle spasms after the procedure and could angle his left hand a little more, although he phoned Guest six months later to say the surgery had not made any permanent difference. On the downside, there were also post-treatment complications: a 22-year-old contracted meningitis, pneumonia and gastrointestinal bleeding, which were managed with heavy medications, and another had a fever and confusion along with a drug rash. Guest is critical of the Chinese stem cell treatments: he believes some doctors are “motivated by profits” and “they place patients at risk for therapies which have minimal effect.”

Eight months after travelling to China, Haas was struggling with the symptoms of Machado-Joseph disease. He was having problems walking and was falling again. The family still had some money left over from their fundraisers, so they decided to make another trip to China, and took out a small loan. In March 2008, he and his wife went to China, this time to Qingdao in eastern China—the first hospital wouldn’t accept them since it was now prioritizing Chinese nationals over foreigners, explains Cherie. After four weeks of treatment, Haas had more energy and there were slight improvements in his balance and speech, he says. However, the gains lasted all of two months and today he’s just as bad as before the first trip. Nevertheless, despite the costs, and the dubious rates of success, the family would like to return again if they could afford it. “I would go tomorrow if we could,” Cherie says. “It gave people hope.”

Day 2 and 3 of the NAF conference

2009-03-29T18:14:00.000-07:00

Apologies for the delay in publishing this post on the rest of the NAF conference; Richard's daughter, Andrea, is guest-blogging this post after catching up with some school work.

The rest of the presentations were particularly informative with Saturday's researchers discussing how to treat the symptoms of ataxia (through medication, diet, speech therapy, etc.) and Sunday's presenters describing the latest progression in mapping the neuropathologies of certain ataxia variants and developing sophisticated new genetic treatments. Saturday's focus for participants was on dealing with the nuts and bolts, educating people with ataxia and their caregivers to manage the effects of the disease. We also learned about a couple of clinical trials, such as an upcoming Chantix trial (yes, the anti-smoking drug) that will soon commence.

Medication management is a particular concern given that improper dosages can cause adverse side effects for people with sensitive nervous systems as is the case for ataxics; when in doubt, start off with the lowest dosage possible and work your way up. Certain symptoms such as fatigue may be drug side effects, rather than a result of the disease itself; if you notice a change in functioning or how you're feeling, take note of any changes in your medications and let your doctor know. Over the counter medications, "natural remedies" and supplements should be reported to your primary care physician and neurologist, too, as these do have biochemical effects that may interact with other drugs that you're taking. Supplements such as antioxidants CoQ10 and Idebenone have been heavily marketed for those with a variety of neurodegenerative diseases, but their efficacy is somewhat questionable at the present, especially given that they are quite expensive.

The highlight of the final day was Dr. Ryan Boudreau's presentation on RNAi for SCA-1, though numerous others such as Dr. Henry Paulson are currently working on RNAi therapies for other ataxia variants. Dr. Boudreau and his collaborators have been testing the delivery of inhibitory RNA that "turns off" the SCA-1 gene producing the toxic protein hastening the neuronal death in the cerebellum. Current issues involve ensuring the safe delivery of the RNAi via a non-pathogenic virus; "more is not necessarily better," as Dr. Bourdreau pointed out, as silencing genes with these engineered RNAi may inhibit other genes not meant to be interfered with. They are also investigating the site of delivery to see if the therapeutic effects can be enhanced by affecting a greater portion of the cerebellum. It will be interesting to see what the long term effects of RNAi therapy are, if the improvement in behavioral functioning as well as in halting the progression of the disease can be upheld.

The quantity of medical information, with one presentation after another, was quite a bit to process although the researchers took great care to make sure that they were clearly communicating the more technical aspects of their presentations. The intellectual sophistication of the conference proceedings gave this college student a mental workout during her spring break, a testament to the researchers' generosity in sharing their findings and willingness to outreach to the ataxia community. I can only imagine how intimidating the volume of neurogenetic and biochemical terminology felt for other laypeople like myself who haven't taken college biology (or don't remember the subject). If I weren't English language proficient and the beneficiary of a good education, I don't think I would've been able to understand even a third of what was presented.

Having these conferences and keeping the ataxia community aware of the latest progress are unquestionably necessary, but we must also consider who within the community is able to absorb the nuances of disease etiology and symptom management, pursue the most effective treatment strategies, and have the means to do so.

With the current economic climate, we suspect that fewer people were able to attend this year's conference. Those weren't able to attend this year, as well as previous years', probably have more limited resources, which may affect their ability to continue managing their ataxia and seek medical help. We wonder about how these breakthroughs in biomedical research can be best disseminated to those affected by ataxia but who are unaware of its progression or even the many avenues for treating symptoms in the meantime.

Ataxia is an equal opportunity disease that affects people of all racial/ethnic and class backgrounds; unfortunately, not everyone is able to receive good care and sufficient support in handling everyday life with this disease. Addressing barriers to accessing medical information, treatment options, and health care in general must become a priority if we are going to help everyone who is affected by this disease. Raising ataxia's profile in the public and medical arena, including through the annual NAF conference, is a crucial first step. We are grateful for the support and advice we have received from fellow participants during the conference, swapping stories person to person about our experiences with the disease, learning from each other about remedies we didn't know about, and finding new sources of hope and inspiration.

We can only hope that this blog can serve at least some small role in disseminating information about ataxia to those in need of it.

Day 1 of the NAF Conference: it’s always drizzly in Sea-Tac

2009-03-20T23:57:00.001-07:00

Andrea is guest blogging with Richard in covering this year’s National Ataxia Foundation conference in Seattle (or more specifically, Sea-Tac, as the city’s mayor kindly pointed out as he welcomed the participants this morning). Spending the latter portion of my spring break here has been as educational as being in class. The opening lecture, reviewing the genetic basis of ataxia, compacted “3 years worth of cellular biology,” in Dr. Perlman’s words. Dr. Laura Ranum used the apt metaphor of drinking from a fire hydrant to describe the knowledge influx in medical research. At the top of the research agenda is integrating the findings from all these molecular genetic and neuropathological studies into understanding how to treat the various types of ataxia.

Ataxia experts Dr. Ranum, Dr. Harry Orr and Dr. SH Subramony, succinctly discussed upcoming trends in ataxia studies, with basic scientific research evolving into transitional research. Ataxia research has promising new avenues for funding, which is critical for these medical investigations to progress. Despite the woes of the current economic climate, the NIH has received an additional $8.2 billion for clinical and translational research, among other areas of medical interest. So far this year, 9 approved research grants, out of 48 applications processed, will be receiving $484,000 from the NAF. Researchers want to capitalize on the $1 million NIH challenge grants with an unprecedented, accelerated funding approval process; these challenge grant studies should be starting earliest 9/30/09. We’ll be staying tuned for tomorrow’s presentations focusing on these individual experts’ upcoming trials and how ataxia patients can become involved.

The conference has engaged much peer-to-peer interaction and education. Researchers lucidly presented this complex material to the general audience of patients and caregivers, as well as updating their fellow experts about developments in the field. Kudos to Corrie Smith’s presentation on genetic testing for being extremely accessible and thoughtful in considering the complexity of ethical implications involved for all parties. The “Birds of a Feather” breakout sessions were particularly valuable, with each session focusing on a different group affected by ataxia so that caregivers, people with SCA 3, individuals with Friedrich’s, etc. could discuss their experiences with each other. In between workshops and presentations participants were mingling with each other, discussing their experiences with various physical therapies, diet/supplement regimens, drugs and other treatments and recommending what they had found effective.

The accommodations at the Doubletree have generally been accessible: the low-pile carpets are wheelchair-friendly, there are plenty of places to sit along the hallway, and most of the workshops have been on the first floor. The booths outside the main presentation area featured all sorts of useful pamphlets and booklets, local support services for Washington area ataxia patients, and opportunities for attendees to participate in some new studies on the spot. If you’re a conference attendee reading this and have some time tomorrow, please stop by UC Berkeley research coordinator Nola Klemfuss’s experimental set up. She’s conducting non-invasive, physically undemanding studies on visuo-motor coordination and could really use some more folks to participate. Compensation is $20/hour, and participation takes about 1.5 hours. Richard participated in her study and can vouch that it’s interesting.

We look forward to keeping you posted on the latest clinical trials and RNAi research in the next two days.

More good news

2009-03-07T15:53:00.000-08:00

"Major advance" reported in stem-cell research

By Karen Kaplan

Los Angeles Times

Borrowing a biological cut-and-paste trick from bacteria, scientists have created the first personalized stem cells for patients that are free of the cancer-causing viruses and genes needed to make them, according to a study to be published today in the journal Cell.

The stem cells, derived from skin samples provided by five patients with Parkinson's disease, were first transformed into the undecided state of cells in an early embryo. Then, they were used to make the dopamine-manufacturing neurons that are lost to disease.

The technique removes a key barrier to using a special class of stem cells called an induced pluripotent stem cell, or iPS cell, to create replacement parts for patients that could be transplanted without any risk of rejection — the ultimate goal of regenerative medicine.

"This is a major advance in the field," said Dr. Marius Wernig, an assistant professor at the Stanford Institute for Stem Cell Biology and Regenerative Medicine, who wasn't involved with the study.

The reprogramming of skin cells into iPS cells, which have the potential to become any kind of cell in the body, is one of the hottest areas of biological research. The cells seem to offer all the benefits of embryonic stem cells without any of the ethical drawbacks. They are also ideally suited to making genetically matched tissues for patients, such as insulin-secreting islet cells for people with diabetes or brain tissue to treat stroke victims.

The reprogramming process requires that scientists turn on a handful of genes that are active during early embryonic development but dormant in normal skin cells. Most researchers rely on infecting the cells with viruses to do this job. But these viruses may also lead to cancer, as can some of the genes used for the reprogramming job.

Dr. Rudolf Jaenisch, a stem cell researcher at the Massachusetts Institute of Technology and the Whitehead Institute for Biomedical Research in Cambridge, Mass., and his colleagues found a way to remove the viruses and genes once their work was done.

They engineered three viruses that contained the reprogramming genes — known as Klf, Sox2 and Oct4 — flanked by pieces of DNA called loxP sequences. After the skin cells were transformed into colonies of iPS cells, the scientists activated a protein that snipped out everything between the loxP sequences.

The technique is commonly used to modify the DNA in cells, and Jaenisch decided to try it with iPS cells.

"We borrowed it from bacteria," said Jaenisch, the study's senior author. "Bacteria need it for certain genetic manipulations."

Hallelujah!

2009-03-06T17:36:00.000-08:00

This just appeared over the newswire:

Source: Obama to reverse limits on stem cell work

By BEN FELLER and LAURAN NEERGAARD, Associated Press Writers

WASHINGTON – Reversing an eight-year-old limit on potentially life-saving science, President Barack Obama plans to lift restrictions Monday on taxpayer-funded research using embryonic stem cells. The long-promised move will allow a rush of research aimed at one day better treating, if not curing, ailments from diabetes to paralysis — research that crosses partisan lines, backed by such notables as Nancy Reagan and the late Christopher Reeve. But it stirs intense controversy over whether government crosses a moral line with such research.

Obama will hold an event at the White House to announce the move, a senior administration official said Friday. The official spoke on condition of anonymity because the policy had not yet been publicly announced.

Embryonic stem cells are master cells that can morph into any cell of the body. Scientists hope to harness them so they can create replacement tissues to treat a variety of diseases — such as new insulin-producing cells for diabetics, cells that could help those with Parkinson's disease or maybe even Alzheimer's, or new nerve connections to restore movement after spinal injury.

"I feel vindicated after eight years of struggle, and I know it's going to energize my research team," said Dr. George Daley of the Harvard Stem Cell Institute and Children's Hospital of Boston, a leading stem cell researcher.

But the research is controversial because days-old embryos must be destroyed to obtain the cells. They typically are culled from fertility-clinic leftovers otherwise destined to be thrown away.

Under President George W. Bush, taxpayer money for that research was limited to a small number of stem cell lines that were created before Aug. 9, 2001, lines that in many cases had some drawbacks that limited their potential usability.

But hundreds more of such lines — groups of cells that can continue to propagate in lab dishes — have been created since then, ones that scientists say are healthier, better suited to creating treatments for people rather than doing basic laboratory science.

Work didn't stop. Indeed, it advanced enough that this summer, the private Geron Corp. will begin the world's first study of a treatment using human embryonic stem cells, in people who recently suffered a spinal cord injury.

Nor does Obama's change fund creation of new lines. But it means that scientists who until now have had to rely on private donations to work with these newer stem cell lines can apply for government money for the research, just like they do for studies of gene therapy or other treatment approaches.

The aim of the policy is to restore "scientific integrity" to the process, the administration official said.

"America's biomedical research enterprise experienced steady decline over the past eight years, with shrinking budgets and policies that elevated ideology over science. This slowed the pace of discovery and the search for cures," said Sean Morrison, director of the University of Michigan's Center for Stem Cell Biology.

Critics immediately denounced the move.

"Taxpayers should not have to foot the bill for experiments that require the destruction of human life," said Tony Perkins of the conservative Family Research Council. "President Obama's policy change is especially troubling given the significant adult stem cell advances that are being used to treat patients now without harming or destroying human embryos."

Indeed, there are different types of stem cells: So-called adult stem cells that produce a specific type of tissue; younger stem cells found floating in amniotic fluid or the placenta. Scientists even have learned to reprogram certain cells to behave like stem cells.

But even researchers who work with varying types consider embryonic stem cells the most flexible and thus most promising form — and say that science, not politics, should ultimately judge.

"Science works best and patients are served best by having all the tools at our disposal," Daley said.

Obama made it clear during the campaign he would overturn Bush's directive.

During the campaign, Obama said, "I strongly support expanding research on stem cells. I believe that the restrictions that President Bush has placed on funding of human embryonic stem cell research have handcuffed our scientists and hindered our ability to compete with other nations."

He said he would lift Bush's ban and "ensure that all research on stem cells is conducted ethically and with rigorous oversight."

"Patients and people who've been patient advocates are going to be really happy," said Amy Comstock Rick of the Coalition for the Advancement of Medical Research.

The ruling will bring one immediate change: As of Monday, scientists who've had to meticulously keep separate their federally funded research and their privately funded stem cell work — from buying separate microscopes to even setting up labs in different buildings — won't have that expensive hurdle anymore.

Next, scientists can start applying for research grants from the National Institutes of Health. The NIH already has begun writing guidelines that, among other things, are expected to demand that the cells being used were derived with proper informed consent from the woman or couple who donated the original embryo.

Call To Arms

2009-02-24T20:29:00.000-08:00

I often wonder about the readership of this blog and if there are any readers at all. To those who peruse regularly and even to those who stumble upon this site by accident, I would like to call your attention to two important events concerning MJD.

Firstly, the National Ataxia Foundation 52nd Annual Membership Meeting will be held next month in Seattle from March 20th to March 22nd. Richard and I attended last year's meeting in Las Vegas and came away learning so much. Needless to say, Richard will not be missing this for the world! It is not too late to register. You can even do that online!

Secondly, we just received Dr. S. H. Subramony's questionnaires in the mail today. Dr. Subramony of University of Texas, who is a renown expert of SCA diseases, is currently conducting a study on MJDers. Those who have registered with the Cooperative Ataxia Registry should have been contacted already to participate in this study. If that is not the case and/or if you would like to find out if Dr. Subramony is still enrolling for this study, please contact him at:

S H Subramony MD

Professor of Neurology

University of Texas Medical Branch

301 University Blvd

Galveston TX 77555

Office 409 772 2646

Fax 409 772 6940

E-mail: shsubram@utmb.edu

The glimmer at the end of the tunnel

2009-01-27T23:29:00.000-08:00

To paraphrase Newton's law of inertia, a blogger persists in a state of rest unless acted upon by an external force (of will power). I have been rather negligent in passing along to the few who read or happen to come across this blog the latest in MJD research.

Here are some very encouraging news from the scientific front-lines, thanks to the MJD Family Board for sharing the information:

RNAi has potential for use in MJD treatment and constitute the first proof-of-principle for allele-specific silencing in the central nervous system

More about the aforementioned research

CATENA^® : a new drug approved for the symptomatic management of patients with Friedreich’s Ataxia which may be beneficial in treating MJD

and lastly

Geron Receives FDA Clearance To Begin World's First Human Clinical Trial Of Embryonic Stem Cell-Based Therapy

On the home front, Richard's hard work at his twice weekly PT is paying off. Today, he was able to go from a sitting position to standing upright unassisted three consecutive times without fumbling or tottering. His movements when using the walker are steadier and more fluid. Small steps but important steps which is all that we are asking for.

The Curious Case of the Naked Man on the Floor

2009-01-06T17:46:00.000-08:00

I've decided to begin the new year with a more light-hearted post. A few days ago, while researching the latest on stem cells on the web, I came across a set of articles (1, 2, 3)from the Charleston Post and Courier about a patient who was at Nanshan Hospital around the same time as we were.

Upon reading the article, I realized that the gentleman in the articles was the same person that I described in my post dated March 27, 2007. These news articles helped me understand better his experience in China. While the hospital staff and the reporter each painted a different picture of this patient's personality and deeds, I am sure that he meant to do no harm. Furthermore, I empathize with his desire and need to do everything within his power to get better.

The famous movie producer, Robert Evans, once said, "There are three sides to every story. Your side, my side and the truth. And no one is lying." I couldn't have put it better myself.

It was the best of times, it was the worst of times

2008-11-23T13:43:00.000-08:00

2008 has been a momentous year so far, filled with both memorable celebrations and challenges that we'd rather do without.

Richard and I celebrated our 25th wedding anniversary and half century birthdays. We also reunited with family members who we have not seen for some time and participated in Richard's mother's 80th birthday bash in New York.

However, our mothers' health problems continue to plague them. Richard also had his share of health issues in the past few months. There were falls and accidents that resulted in trips to the emergency room. The numerous stitches on his face has given him a "tough guy" aura.

Looking beyond our immediate family, we now have a charismatic African-American president-elect who is poised to bring much needed change to the nation. However, the economy has plunged into unprecedented chaos that threatens the livelihood of every global citizen.

It is hard to remain positive in these difficult times. I take comfort in Nietzche's quote of "that does not kill us makes us stronger".

More from ACARM7

2008-10-12T20:50:00.000-07:00

We saw Dr. Perlman recently when Richard had his semi annual checkup with her at UCLA. I asked Dr. Perlman for a copy of her ACARM7 talk since I was only able to summarize a small portion of her presentation in my last post. Aside from news of the latest trials for HD and SCAs, it has pointers and information germane to the SCAs.

Mazel Tov to Dr. Perlman who was presented with the prestigious Sherman M. Mellinkoff Faculty Award this past May. The award is considered the highest faculty distinction at the UCLA Medical School.

Notes from ACARM7

2008-09-14T19:42:00.000-07:00

We just came back from the 7th All California Ataxia Research Meeting (ACARM7) held at the San Jose Doubletree Hotel today. This year's meeting was almost canceled due to budget issues stemming from lower than expected attendance. At the eleventh hour, it was saved by a generous anonymous underwriter. The other unsung heroes are Mike Fernandes, the organizer of the venue, the doctors and presenters of the program and the numerous volunteers who helped to bring the event into fruition.

The first speaker of the morning was Dr. Richard Ivry who talked about "The Effect of Ataxia on Cognition". Specifically, he spoke about Dr. Jeremy Schmahmann's work on the "Cerebellar Cognitive Affective Syndrome". Dr. Ivry concluded that ataxics have difficulty with non-motor tasks but their cognitive problems might be secondary to their motor problems.

Dr. Susan Perlman was next. Her topic was "An Update of Clinical Trials for the SCAs and HD". According to Dr. Perlman, if one were to do a web search on the key words "clinical trials for Ataxia", one would find 42 trial listings of which only 35 actually dealt with Ataxia. 13 of these trials have been completed, 5 are active but no longer recruiting for subjects while the remaining 17 are still recruiting. Of these 17, one is available in California ---- Phase III Idebenone and Extension Study for FA. (Friedreich's Ataxia) Also, the pilot study of Lithium for patients with SCA1 has now started in Maryland and is still recruiting.

Dr. Lisa Ellerby followed Dr. Perlman with "Target Validation in HD: siRNA screens in HD cell culture models". After conducting studies to screen through possible druggable targets using siRNA technology, her team has found that HDAC4 inhibitors to be effective against Huntington's Disease.

Dr. Elizabeth Thomas was the last speaker of the morning. She further elaborated on the HDACs with "Novel Histone Deacetylase Inhibitors as Therapeutics for Triplet Repeat Disorders". While conventional HDAC inhibitors (used in treating cancers) are very toxic, novel HDAC inhibitors have been shown in (non-human) trials to be low in toxicity. Experiments on transgenic mice using HDACi4b have shown it to be therapeutic and non toxic for triplet repeat disorders such as HD, SCA1, 2 and 3. Repligen Corp. in Waltham, Massachusetts has licensed HDAC inhibitors in development.

The three presenters in the afternoon were Richard Devylder, (Emergency Disasters for the Disabled) Colleen Campbell (Falling Prevention) and Arya Pathria. (Laughing: Laughter Yoga Workshop)

Finding your inner Tigger

2008-08-01T19:19:00.000-07:00

Just in case you missed "The Last Lecture", I highly recommend it on those "why me" days.

All California Ataxia Research Meeting 2008 (ACARM7)

2008-07-09T17:31:00.000-07:00

ACARM7 will be held on Sunday, September 14, 2008 at the Doubletree Hotel by the San Jose Airport. This year's meeting will concentrate on the SCAs. Richard and I are looking forward to the event. As usual, kudos to Mike Fernandes for putting this together.

Sad news

2008-07-09T16:58:00.000-07:00

Our friend and fellow Nanshan patient, Nadia, succumbed to ALS in late June. We will miss her terribly but we take comfort in our fond memories of the time that we spent with her in Shenzhen last year. Our deepest sympathy to Fabio and his family.

Please help in finding a cure for this terrible disease by donating to the ALS Association.

Point/Counterpoint

2008-05-25T15:45:00.000-07:00

Remember the NPR article about China stem cells that Richard mentioned in this post? Here's Jake Young's opinion of the article from his blog, Pure Pedantry. He also briefly mentioned and quoted from the Jane Qiu's Lancet Neurology article.

The Lancet Neurology February 2008

2008-05-22T21:12:00.000-07:00

Freelance journalist and neuroscientist, Jane Qiu, interviewed Richard last year about his experience at Nanshan. Her article, "Injection of hope through China's stem cell therapies", was published in the February 2008 issue of the Lancet Neurology.

Thank you, Jane, for making your article available to us.

Download the Lancet article through here

A Spoonful of Sugar

2008-05-15T00:41:00.000-07:00

We just returned from a visit with Dr. Perlman last Friday at UCLA. Richard's SARA score stayed pretty much the same which is encouraging.

Dr. Perlman wanted Richard to start taking a new supplement called Trehalose which is a sugar derivative. Trehalose has been shown to help with Huntington's Disease in preventing the clumping of proteins in the cells. One of the hallmarks of MJD is also clumping of the proteins so Trehalose should theoretically help stop this. Moreover, Trehalose is fairly safe with few side effects and is very cost-effective and readily available.

Here's a link to the website of Neurocoat which is a 100% Trehalose supplement. This article has details on the recommended dosage. We have already placed our order.

A 1,000 Words

2008-04-13T00:31:00.000-07:00

I recently found this photo at the Ride Ataxia website. Kyle Bryant, an extraordinary young man who has Friedreich's Ataxia, is raising money for research and awareness of FA through this website. Please give him your generous support.

Here's a "Where's Waldo" moment. Can you spot Richard in the photo above? It was taken last November during the ACARM6 in Orange County. Kyle came by and he took a group photo with the "Ride Ataxia" banner. Give up? That's Mike Fernandes (in dark blue) at the left end of the banner and Richard (in a yellow shirt with a blue jacket) at the right end of the banner. The Poors (Sally and Kim) are at the extreme right in the back row. I am to the immediate left of Sally and Dr. Perlman (only partially visible) is to my left.

Vegas redux

2008-04-11T17:21:00.000-07:00

On this last trip to Vegas, we decided to tack on a few days before and after the NAF Meeting as part of our 25th wedding anniversary celebration. I've always been fascinated with Las Vegas ever since my first visit there 34 years ago. Since then, I've been back many times, courtesy of my late father who was a gambling aficionado.

Armed with the wisdom and advice of Ricardo Rodriguez, a frequent visitor to Las Vegas who has first-hand knowledge of the ADA-compliant hotel rooms of the city, we split our visit at three different hotels, the Bellagio, Flamingo and Wynn. The result was somewhat of a revelation.

After flying into McCarran, we marvelled at the ease, accessibility and friendliness of the airport facilities and staff. It was a breeze to hail a cab to get to the Bellagio Hotel. I guess the fact that Richard could transfer easily from his wheelchair to the cab made a big difference.

We booked our room at the Bellagio through David Ourisman, a travel agent who is affiliated with Virtuoso, and received extra perks during our stay there. These included continental breakfast for two each morning and complimentary room upgrade when available. However, the nicest "freebie" was the $85 dining (lunch only) credit at Sensi, an Asian-fusion restaurant located inside the hotel. We had already planned on eating at this restaurant so this gift was more than welcomed.

Our room at the Bellagio was very spacious and elegantly appointed and had two Queen size beds. It was located in the new Spa Tower. The view (parking lot) was nothing to write home about but we were willing to settle for a no-view room on a low floor for immediate occupancy since we checked in early and Richard was tired and wanted to nap. The bathroom had a good layout and an enclosed roll-in shower with a fold-down bench. The water pressure from the hand-held shower was very good. The only complaint is that the glass door to the shower was very heavy and awkward to operate for someone in a wheelchair. Ricardo mentioned that Bellagio also has rooms with Hoyer lifts for folks who need them.

We moved across the strip to the Flamingo Hotel in time for the NAF meeting. We got a newly remodeled Austin Power-ish "GO" room with a platform King bed, roll-in shower and an unbelievable view of the famed Bellagio fountains. The room was smaller than our room at the Bellagio but the roll-in shower was the best designed ADA shower in a hotel that we've ever encountered. Instead of the usual heavy glass door, this one had a shower curtain that was effective enough to keep the floor in the rest of the bathroom dry. The digital TV embedded into the bathroom mirror was another nice touch.

After the NAF meeting wrapped up on Sunday, we spent one day and night at the Wynn hotel. The plushiest of the three hotels, it also had the prices to match. The palatial room had two Queen beds and an enormous bathroom that echoed with our footsteps. The bathroom had both a roll-in shower and a bathtub with jets. It also had two sinks and a mini TV built into the wall. Unlike the Bellagio, the Wynn loaned Richard a wheelchair without requiring a credit card imprint from us. We were also informed by Cyndi Segroves, one of the speakers at the NAF workshops, who stayed at the Wynn during the meeting that the Wynn also has rooms with Hoyer lifts.

Overall, we were very impressed with the three ADA rooms that we stayed at during the trip. Any one of the three would more than meet our needs. The bottom line is then a matter of cost. Here's the break down:

Bellagio: We paid $206 before taxes per night for 2 nights. This was the "Virtuoso" rate during that period. However, we received "bonuses" worth $141. ($28 credit per day for breakfast for 2 days and a $85 dining credit at Sensi) Subtracting this amount from the room rate, it came to around $136 per night, excluding taxes.

Flamingo: We originally reserved a standard room at the NAF group rate of $124 per night before taxes. However, we opted to upgrade to the "GO" rooms at the last minute when we were informed by the check-in clerk that some of the "GO" rooms were ADA compliant. We were previously told when we called up to reserve the room that none of the "GO" rooms were handicap accessible. The upgrade cost an extra $44 per night, making the grand total $168.

Wynn: I booked the room directly from the hotel at a special promotional rate of $199 per night before taxes. This included a $100 resort credit that is good for dining at the hotel's restaurants, shows or spa expenses. Since we only stayed one night and had already planned to dine at the hotel, our out-of-pocket for the room was $99.

The moral of the story is that 4 star properties are more affordable than you think. It really depends on what you are looking for or what services you value. And then, there are the intangibles. The Flamingo is young and boisterous with girls and boys with spiky blue hair that woke us up three in the morning with their drunk hollering and running up and down the hallway on our floor.

This post is by no means an endorsement for any of the three hotels mentioned. I am merely sharing our experiences and observations on this trip with you. If you should happen to use the above information as a reference, please beware, as Richard is fond of saying, "your mileage may vary".

National Ataxia Foundation Annual Membership Meeting 2008

2008-04-09T16:29:00.000-07:00

Thanks to the folks from the Arizona Ataxia Support Group, the NAF Annual Membership Meeting held in Las Vegas last month went off without a hitch. The event lasted three days with work shops, speakers, a silent auction and an evening banquet. We, as first timers, thoroughly enjoyed ourselves while meeting other ataxians and their families. Along the way, we saw Dr. Perlman and Mike Fernandes. Here are some of the highlights:

Friday, 3/28, started out with different workshops in the morning. We attended the following:

"Speech & Swallowing" with Gail Lommen who is a Speech Language Pathologist. She suggested the Lee Silverman Voice Treatment in helping with speech problems.

"Accessible Travel" with Cyndi Segroves, a travel professional who herself is mobility-impaired and uses a power wheelchair.

"Dancing with Ataxia" with Thomas Clouse, MD, who himself has ataxia but is able to walk with a normal gait and even dances on a regular basis. He shares his insight on how to regain the ability to walk. We were so impressed by what we saw that we purchased his instructional CDs.

The afternoon was devoted to "Birds of a Feather" meetings for ataxians, parents of ataxians and caregivers/spouses of ataxians. This is a time for people with the same type of ataxia to meet in small, informal groups to discuss and share their experiences and concerns of the disease.

Saturday, 3/29, the day started with talks and presentations by doctors and researchers on the latest about ataxia. Dr. Huda Zoghbi who, together with Dr. Harry Orr, first identified the SCA1 gene in 1993, spoke on "Translational Studies in Spinocerebellar Ataxia". In the middle of her presentation, I had a distinct sense of deja vu. I was convinced that I've seen the research on the mice before, but where? Then I recalled this post that I did back on September 30 last year. Unbeknownst to me at the time of that post, the speaker on the Youtube video was Dr. Huda Zoghbi! It was, however, much more exciting to hear Dr. Zoghbi speak in person.

The last person to speak that morning was Dr. Chip Wilmot. He spoke about "Ataxia Patient Registries". In order to facilitate both researchers and patients with ataxia in obtaining up to date information on the disease, it is vital that all ataxians register themselves with the Cooperative Ataxia Registry. As of now, only 370 people have registered. One of these 370 is Richard. 36 of these 370 people have SCA3. We are sure that there has got to be more than 36 MJD-ers in the United States alone. Please consider registering if you're an ataxian. Dr. Wilmot will be happy to answer any of your questions regarding the registry at:

Emory Ataxia Center
404-728-4782 (direct line, please ask for Cathy Wood)

Doctors Wood, Subramony, Schmahmann, Orr and Fahey spoke in the afternoon session. We feel privileged to actually see and meet researchers (Subramony & Orr) whose picture and articles appear regularly in Generations at the meeting.

The silent auction and NAF banquet rounded out the evening.

Sunday, March 30, our beloved Dr. Perlman started the morning with her presentation "FRDA Clinical Trials". Her talk was not just about Friedreich's Ataxia alone. She spoke at length on the most recent clinical trials on different types of ataxia and issues pertaining to clinic trials in general. She reminded people to do their part by registering with the Cooperative Ataxia Registry. For more information about ongoing clinical trials in the U.S., please go to:

www.clinicaltrials.gov

Dr. Arnulf Koeppen spoke about "Brain Tissue Repair in Herediatary Ataxia". He was followed by Dr. Broyna Keats who talked about "RNAi Research". Dr. Keats wittily called her speech "Shooting the Messenger". RNAi refers to the method of RNA interference to silence or prevent the mRNA (the "messenger" RNA) of a certain gene or genes from being expressed. Doctors Andrew Fire and Craig Mello were awarded the Nobel Prize for Medicine in 2006 for their discovery of RNAi. I wrote about our recent encounter with Dr. Fire here. Dr. Keats also told the audience that there is already an experiment done on SCA1 infected mice using the RNAi technique. This is encouraging news indeed even though human trials are in the very distant future.

The three day conference came to a close by early afternoon on Sunday.

We were told, unofficially, that next year's NAF Annual Membership Meeting will be held in Seattle, WA. See you then!

Beike Stem Cell Media Publicity

2008-03-19T17:48:00.000-07:00

A friend, Nick, who I met while at Nanshan, gave me a pointer to a recent NPR Article. This makes me think of the various efforts to report on this medical tourism phenomena. I know I've been contacted by journalists from Forbes, Associated Press, the UK. We've also seen publicity from ABC Night Line, an Australian web column, etc.

I applaud these efforts to publicize this phenomena. I hope that the media can present a balanced view of matters. This is all the more imperative given that dissenting views do exist from patients, despite what Beike may say.

Out of the mouths of babes

2008-03-05T22:36:00.000-08:00

Richard and I just returned home from Professor Christopher Scott's stem cell class at Stanford University. It was an honor to be asked to speak to his class about our experience in China. We learned a lot about the subject of stem cells by taking his course last summer.

We recently came across an article about China stem cell treatment co-written by AP reporter Alan Zagier. Mr. Zagier contacted Richard last May to ask him about our trip to China. What is even more interesting is a commentary on Mr. Zagier's article posted on this blog. I was both surprised and delighted to learn that the author of this insightful piece was a 10th grade student. The blog is the product of a school project and the posts written by "the brilliant minds of Jesse's 10th grade World History class."

News from Bergamo

2008-02-28T00:18:00.000-08:00

We recently received an email from Fabio about his blog on ALS. We met Fabio and his mother, Nadia, at Nanshan Hospital last year. Nadia has ALS and underwent stem cell treatment at the same time as Richard. Despite the language difficulty, it was easy to quickly warm up to this nice family. We think of them often.

ABC Nightline 2/15/08

2008-02-27T23:34:00.000-08:00

Our friend George sent us this link to a recent ABC Nightline story on stem cell treatment in China. Here's the video link to the same story.

Update on PhosChol

2008-01-21T17:11:00.000-08:00

Richard has taken the PhosChol supplement for a month now and unfortunately has not noticed any substantial improvement. He'll finish the bottle but will probably not order any more. The consensus among the folks on the MJD board who volunteered to be the PhosChol guinea pigs is that the supplement has not brought about a measurable change.

Viva Las Vegas

2007-12-24T01:33:00.000-08:00

Merry Christmas everyone! We were in Las Vegas last week shopping for holiday gifts, taking in a show and doing some ground work for the Annual Membership Meeting of the National Ataxia Foundation. The event will be held at the Flamingo Hotel in Las Vegas from March 28th to March 30th, 2008. We wanted to see how accessible Las Vegas is, and in particular, we were interested in the facilities and configuration of the ADA hotel rooms.

In general, Las Vegas is probably one of the most accessible cities that we've ever visited. We've never seen more folks on wheelchairs and scooters, and they all seem to be having a great time. At the airport and cab stands, it seemed like every 4th or 5th taxi has the handicap accessible sign on the side of the cab. All big hotels have a fleet of scooters by the bell desk ready. Renting the scooter merely requires signing it out with the bellman. All of the public restrooms that we've used are handicap accessible as were the bathrooms and showers in most hotel spas. The elevated walkways at major intersections on the strip have elevators large enough for both wheelchairs and scooters. The monorail and trams are also accessible with space to accommodate even scooters. We were very impressed.

OK, enough PR for Vegas. Here's what we don't like about Vegas:

1. Can the casinos switch to a low pile carpet in the public areas? It was very tiring to get around the carpeted areas in a manual wheelchair. We (Andrea and I) pushed Richard around, and it tires us out after a while. Can you imagine Richard pushing himself around? Even though we don't gamble, in order to get to the room elevators, you have to snake your way around the entire casino floor. The layout of the casino can be very unfriendly for folks in wheelchairs because the hotel deliberately put slot machines in odd angles so that you have to squeeze around chairs to get from point A to point B.

2. Cigarette (second hand) smoke and an apparent dearth of ashtrays. Need I say more?

3. Why do hotels place their handicap accessible rooms in the most undesirable areas of the building? OK, I understand that the room must be close to the elevator, but does it have to face the freeway, the noisy delivery dock or the electric transformer that emits a bone-vibrating hum 24/7? I dare you to find a handicap hotel room in Vegas that has a view of the Strip! I was told that the only rooms of this kind exist at the Wynn Hotel. If only it didn't cost an arm and a leg ......

For those who are interested in attending the NAF Annual Meeting, you'll be please to know that the Flamingo has ADA rooms available at the rate of $124 per room per night. These go quickly, so be sure to make your reservation soon.

Role Model

2007-12-03T17:18:00.000-08:00

Stem cells, experimental drugs and other curative treatments aside, here's the inspirational story of Charlie Wedemeyer and his fight against ALS.

Life isn't measured by the number of breaths you take

2007-12-01T17:24:00.000-08:00

One of the biggest obstacles in raising funds and awareness for Ataxia is the fact that the number of people afflicted with the disease is minuscule compared with say, cancer or diabetes. Similarly, drug makers would rather direct their attention to researching cures for cardiovascular diseases than orphan ailments like SCA3. I recently came across an article in the Wall Street Journal that talked about one man's attempt in turning the tide on funding and finding the cure for ALS.

Speaking about spreading awareness of rare diseases, on an episode of House on TV a few weeks ago, a doctor confessed that she might have inherited Huntington's Disease from her mother. She refused to be genetically tested because "not knowing her fate encourages her to live life fuller." Although I do not agree with this character's reasoning, I do applaud her for wanting to live her life to the fullest despite her potential handicap.

On the home front, Richard is keeping up with exercising, eating right and taking various medicines and nutritional supplements prescribed and recommended to him. Lately, he has found a local physical therapist who has experience working with patients who has neurological ailments. In fact, the PT's father has MS so he is intimately familiar with this class of disease. Richard described his weekly 40-minute PT sessions as "brutally intense". Perhaps PT in this case means "physical terrorist"!

Through the MJD discussion group came news of a new nutritional supplement regime that has shown promise in improving ataxia symptoms. A few members on the MJD discussion group, including Richard, have volunteered to be the guinea pigs who will then keep tabs of their experiences and results of the supplement and report back to the group. Richard's initial efforts were hampered by the fact that we ordered the wrong type of Vitamin B. This has been corrected and he will start taking the correct Vitamin B and PhosChol starting next week. Also, we learned that in order to get the optimal results, the supplements cannot be taken in conjunction with any anti-depressants or any drug that affects the CNS (Central Nervous System). Wish us luck!

The Accidental Blogger

2007-11-20T16:53:00.000-08:00

We are honored to be asked recently by Prof. Christopher Scott of Stanford University to write a guest post on his blog, The Stem Cell. We had a difficult time writing the post because we've always felt rather uncomfortable when asked to give our advice on whether or not to go to China for stem cell treatment. On one hand, we don't want to appear standoffish by refusing to take a position but on the other hand, it is rather presumptuous of us to think that we're even qualified to lend our opinion on such sensitive and personal issues as someone's health and well-being.

News from Down Under

2007-10-20T21:08:00.000-07:00

We were alerted to an article in 6minutes.com titled "Hard sell on Chinese stem cell cures" that commented on my post about ethics.

Visit to Southland

2007-10-19T17:43:00.000-07:00

We've just returned from visiting Los Angeles and Irvine this past week. Coincidentally, it is USC's Trojan Parents' Weekend so we got to spend some time with Andrea.

It has been six months since we've returned from China and time to see Dr. Perlman at UCLA for another evaluation. We have been told by Beike that we should be seeing some improvement (if any) by six months, if not before. On this visit, Richard lost a few points on his SARA score compared to his May 2007 exam. His speech, hand-eye coordination and foot-shin test were a little worse. However, Dr. Perlman remarked that Richard looked very alert and healthy. His energy level and stamina remain good. Furthermore, Dr. Perlman shared with us news that there are at least two exciting medical trials for Ataxians that will be upcoming in 2008. It is therefore important for SCA-ers to get registered with the Cooperative Ataxia Registry in order to become part of the database of patients. We are eagerly waiting for further news in the coming year.

While at Dr. Perlman's waiting room, we saw Mike and Jody from the Northern California Ataxia Support Group. Like us, they were taking advantage of the fact that ACARM is in Irvine this year to piggyback their medical visit with the conference. Speaking of ACARM (All California Ataxia Research Meeting ) 2007, the topics were germane and informative and the speakers lucid and knowledgeable. The audience was smaller than expected but those who came were very dedicated. There were quite a few who had traveled far. One person came all the way from the UK. Two of the non-Californian attendees were Kim and Sally Poor from Arizona. We have never met the Poors although we were familiar with Kim's blog and his experience in China which helped convince us to give stem cell therapy a try. It was good to finally meet them in person.

Of Mice and Men

2007-09-30T19:11:00.000-07:00

Since this is Sunday, I'll take a break from speechifying and let this YouTube video do the talking. I bet the audience would not be laughing if they were watching three people on the spinning rod instead of three mice. Here's another one about this type of experiment.

On another note, I found out as I was looking for additional YouTube videos about SCA that there is an experimental rock group called Ataxia. If a punk rock group can call themselves the Dead Kennedys, I guess anything is up of grabs.

International Ataxia Awareness Day

2007-09-20T12:32:00.000-07:00

Next Tuesday, September 25, 2007, is International Ataxia Awareness Day. The purpose is to create awareness of this relatively rare disease. I am getting a head start in doing my part by posting to this blog in the hopes that you will click here to learn more about Ataxia and how you can help in this effort.

Please consider making a donation to the National Ataxia Foundation by clicking here. Your gift will help Richard and others suffering from this terrible disease through funding the research needed to find the cure. Thank you for your support.

In terms of Richard's progress, there's not much change. He has recently started to work at home with a personal trainer once a week on additional exercises to strengthen his muscles. Despite Richard's diligence in working out at home, at the Y and at his weekly Pilates sessions, he has found that his muscles are getting weaker. Moreover, his sleep has been poor lately due to night terrors. He'll probably ask Dr. Perlman if there's medication for the night disturbances.

An evening with Dr. Andrew Fire

2007-08-18T17:31:00.000-07:00

We're back from Vancouver. It is good to be home. Having traveled quite a bit in the last three weeks, we've become more aware of how airports and airlines differ in accommodating people with special needs. Hong Kong, Burbank and San Jose airports are amongst those that are the friendliest with the best wheelchair attendants. Southwest Airlines deserve special mention for going the extra mile for disabled passengers. We've flown with Southwest more times than we can count and each time, they have been unfailingly helpful, courteous and unobtrusive, on top of that they also offer $49 fares to LA.

In contrast, at both JFK and Vancouver, our wheelchair attendants were no-shows while at SFO, we had to push Richard up a very steep ramp and then waited from another 20 minutes for the wheelchair attendant to appear. While generally it is possible to push Richard around most airports through security checks, departure gates and baggage claim, there are airports, JFK being the most notorious, where in order to get to the elevators to go down to baggage claim and transportation, one needs to go behind and into restricted areas. This is where the wheelchair attendant becomes vital since he/she has the proper i.d. or key to operate the elevator. Enough of my ranting ....

Richard and I recently heard Dr. Andrew Fire speak on his research on RNAi. Dr. Fire, together with Dr. Craig Mello, received the 2006 Nobel Prize for Physiology or Medicine for the discovery of RNA interference (RNAi). RNAi is a means to "silence" the messenger RNA (mRNA) from giving instructions to make a certain protein. In the case of Polyglutamine Diseases, (including Huntington's, SCAs 1, 2, 3, 6, 7 & 16) RNAi therapy can potentially be used to stop the mutant gene from being expressed. As promising as this breakthrough discovery is, Dr. Fire cautioned that it would take many years before RNAi therapy can become a practical reality. He said that the human physiology is much more complex than that of the C. elegens, a nematode worm, which was his research subject in the RNAi experiment.

You can find the link to his Nobel lecture of RNAi here. Although we probably understood less than half of the highly technical material that Dr. Fire presented, his passion and enthusiasm for the subject matter is easy to see.

Persona non grata

2007-08-09T13:31:00.000-07:00

It's official --- the pointer to our blog has been removed from the stemcellschina.com website. Thanks to our friend Nick who brought this to our attention.

An apology

2007-07-20T10:29:00.000-07:00

I want to apologize to the ex-Nanshan patients to whom I've e-mailed requesting their opinion on the last post concerning ethics. In hindsight, I was most insensitive and inconsiderate in putting them in an awkward and no-win situation by asking them to either support my view or Mr. Hakim's. Mea maxima culpa.

A question of ethics

2007-07-19T02:55:00.000-07:00

I had an interesting discussion with Jon Hakim, director of the foreign patient services department at Beike Biotech today about ethics. On several occasions, Jon e-mailed us with requests that we did not comply with because we deemed them unethical and improper. Jon, on the other hand, thinks that these requests were reasonable. So to settle this debate, we agree to poll this audience or, more specifically, the folks who have received treatment in Nanshan. I will forward the contents of this post via e-mail to the Nanshan patients whose email addresses I have. I welcome the opinions of the readers of this post as well.

Point 1: Is it ethical for Jon to ask Richard to post the actual medical report of his visit with Dr. Perlman this past May when Richard was given the SARA (Scale for the Assessment and Rating of Ataxia) which quantified his progress after the stem cell treatment? Jon made this request after he read our May 9 post about the results of the test. We had never given Jon any indication that we would be open to sharing Richard's medical records and reports publicly nor did we ask for his input on our visit with Dr. Perlman. We received his e-mail on May 16, which reads:

I was wondering if you could post the medical reports that you have gotten from Dr. Perlman on your web site? It would add some credibility to it, I believe. Thank you.

We responded by saying that we would not because the information is private. We have already stated in our blog that there was measurable improvement. Why do we, the patients, need to lend "credibility" to the clinical assessment? Who is going to challenge our word? The purpose of our blog is to keep our friends and relatives abreast of Richard's progress. We are not in the business of proving or disproving that the treatment works nor are we hawking Beike's stem cell treatment.

Jon countered that various patients, including Kim Poor, have expressed their desire to post their medical records publicly to substantiate the effectiveness of the treatment. Since we have posted Richard's numerical SARA score in our post, Jon assumed that it was OK for him to ask us to post the actual medical report.

My problem with Jon's request not only stems from his casual treatment of such personal information but that the request came from Beike and not the Nanshan doctors. Isn't there a conflict of interest here? What would possibly justify the need for the representative of the company that sells the treatment to ask for medical data directly from the patient? Isn't this the domain of the doctors at Nanshan? In the US, medical institutions must follow specific guidelines to ensure the confidentiality of patients' medical records (HIPAA). Not only that, but there is strict protocol about who should and should not contact the patient in clinical trials so as to safeguard the impartiality of the data and experiment.

Point 2: When we returned from China, we were scheduled to see Dr. Perlman for a post-treatment consultation on May 7. As we mentioned in our May 1 post, Richard had sprained his foot in late April. We received an e-mail from Jon on May 4, asking us to consider postponing our visit with Dr. Perlman for another week because, in Jon's exact words, he wanted the doctor to see Richard on "an up day instead of a down day."

Since we live in the San Francisco Bay Area, and Dr. Perlman is at UCLA in Southern California, a last minute change in plans (2 days notice and on a weekend) translates into time and money lost in rescheduling flights and lodging. Moreover, the lead time to get an appointment to see the doctor is easily 2 to 3 months. Those who have traveled with a disabled companion understand the complicated logistics involved in not only packing for special needs but also arranging for other specific accommodations and reservations necessary to make such travel happen. A request that would disrupt such carefully laid plans should not come lightly and without good cause.

Would delaying Richard's visit a week have a significant effect on the accuracy of the SARA score? I don't know. I do know that Dr. Perlman emphasized before our China trip that it was very important for her to examine Richard as soon as we returned in order to measure his progress. Our May 7th visit was almost a month after we had left Nanshan. Kim Poor wrote in his blog that he saw Dr. Perlman as soon as he deplaned in Los Angeles from China.

Would Jon have cause to ask Kim to postpone his visit if he had known that Kim was going to see Dr. Perlman after a long and tiring plane ride? How would jet lag impact Kim's performance during Dr. Perlman's examination? If Jon had made this request to him, would Kim have complied? Are these questions even relevant since a physician is trained to take into consideration how factors like travel, a sustained ankle sprain or fatigue might affect the performance of the patient?

One thing on which Jon and I agreed is that his e-mail telling us that he would rather us not mention about the recent Wall Street Journal article here on our blog is ethically questionable. His e-mail further said that "the WSJ is evil, especially that reporter." In another e-mail, Mr. Hakim commented that "this journalist in general is well known to spin his stories anti China as much as possible and I had firsthand experience." Not only did I mention the article in the blog but I also wrote this. I believe in presenting both sides of the story and letting the reader decide.

I cannot shake the feeling that Big Brother is watching. Is Jon using our blog to monitor us? I'd like to believe that he is interested in Richard's health as a friend and not as a salesperson of stem cell treatment. However, some of his requests can be construed as too self-serving.

Simply put, we believe that our medical records are private and should only be shared on a "need to know" basis with people who are empowered and qualified to tend to our welfare. Beike should not make unsolicited suggestions and requests to the patients in matters pertaining to the patient's medical decision-making process such as the disclosure of medical reports and physician visits.

What do you think? We'd like to hear your perspective.

Everything you've always wanted to know about stem cells

2007-07-11T15:45:00.000-07:00

Richard and I spoke to our stem cell class at Stanford this past Monday. Each week, Professor Scott asks for student volunteers to make short (10 minute) presentations on any topic pertaining to the subject of stem cells. We spoke about our experience in China, and the response from the class was tremendous - our 20 minute presentation ran over an hour. Afterwards, Professor Scott wrote about it in his blog here.

For those who want to learn more about stem cells and the latest technological advances in this area, there are free podcasts of each week's class on iTunes. Go to iTunes, click on iTunesU, then choose Stanford University, click on "Straight Talk About Stem Cells." If you have trouble accessing iTunes, Professor Scott's book, Stem Cell Now, is a great source in understanding the basics of stem cells. We read this book in the class.

Afterward our representation, many people thanked us, but we really should be thanking them for letting us share our experience and for their insightful, perceptive questions. Some of our classmates work in the medical field while others are teachers, engineers and researchers. Most have a good understanding of stem cells. Here is a sample of some of the Q&As:

Q. Did the Chinese doctors follow up with Richard after he was released from Nanshan Hospital?

A. No. We were given a discharge report with no specific instructions on how or when to follow up. We were, however, told that we could contact the hospital staff should we have any questions or concerns.

It is standard medical protocol in the U.S. for doctors to follow-up on the patient's progress after the patient is discharged from the hospital. This typically involves medical prescriptions, instructions on follow-up care and a check-up appointment with the doctor. So far we have not been contacted by the Nanshan doctors, but we have received a group email from a U.S.-based Beike representative asking Richard about his progress.

Q. How did we hear about stem cell therapy at Nanshan? What studies or reports did we read that convinced us in going to China?

A. We heard about Nanshan from fellow MJDers' experiences. There were no formal medical studies or reports published or provided by Beike about the Nanshan stem cell patients that we were aware of. We researched Beike's website, sent an inquiry to Beike and corresponded with their staff. We accept the fact that we had no guarantee that the treatment was going to work.

I distinctively remember cringing as I listened to my answer to this question. Did we sound desperate and naïve? There is so little that is published about Chinese clinical results that prospective patients mostly rely on anecdotal evidence from stem cell blogs like this one and others at stemcellschina.com. In the package of materials provided by Beike to prospective patients, there was a list of publications by Dr. Yang Bo of Nanshan Hospital, but none of these papers are easily accessible (outside of China). My suspicion is that even if they were available, the text would be in Chinese.

Q. (Directed to Prof. Scott) Were there any representatives from China at the Annual Meeting of the International Society of Stem Cell Research in Cairns, Australia last month?

A. No. The organizers have hoped that by holding the meeting in Australia that it would encourage more participants from Asian countries. Japan was well-represented.

There was some speculation from the class as to why China did not participate. One classmate who is ethnic Chinese suggested the language barrier might be a factor. Perhaps Chinese researchers and doctors are not fluent in English and thus not confident in presenting their work in English. Perhaps, she also hypothesized, their non-attendance can be attributed to the traditional Chinese belief that one should not toot one's horn for fear of being called immodest. I subscribe to the former argument.

I can understand why there is so much skepticism about stem therapy in China. The burden of proof as to whether or not the treatment works has shifted to the patients and not the Chinese doctors or researchers. Patients write about their experience and progress through blogs that are used as anecdotal testimonials. The patients then cite reports of medical visits with doctors in their home countries to further support that there is measurable improvement. In contrast, Chinese doctors seem disinterested in documenting and following up on their patients. This curious lack of interest and initiative on China's part may lead the West to believe that China has something to hide. If the treatment works, then why not show the world solid empirical data instead of relying on soft anecdotal support? Patients can talk themselves blue in the face about how they think the treatment worked for them; unless the Chinese are willing to subject the trials to peer review, however, the treatment will never gain any legitimacy in the West.

Someone in class asked us if we had any regrets about going to China. We told her that we had no regrets whatsoever because we entered into this venture without any expectations of a miracle cure. I still believe that stem cells are the future of medicine. There has been much finger-pointing about how the West is determined to short-change China's efforts. As an ethnic Chinese, I want China to succeed in becoming a premier provider of stem cell therapy. But it is not going to get there without self-advocacy and opening itself to Western scrutiny. There needs to be more effort in the documentation, disclosure and discussion of its clinical experiments. If China wants its accomplishments to be recognized in the West, she must abide by the same protocol and regulations of the Western scientific community, particularly peer review. I can only hope that discussion on blogs like these and in other forums will help facilitate greater cross-cultural understanding and dialogue on stem cell treatments.

Conspiracy Theory

2007-07-03T12:20:00.000-07:00

According to an email we received today from a Beike administrator, the WSJ piece on Chinese Stem Cells published yesterday both misquoted and mis-represented the comments made by Ms. Bogert and Ms. Nguyen, the mothers of the boys treated at the Shenzhen Nanshan Hospital.

There is already enough controversy over the ethics of stem cell therapy before calling into question the legitimacy and effectiveness of the institutions offering such treatments. Most people acknowledge that such treatments exist in bona fide hospitals administered by credentialed physicians. However, the jury is still out on the effectiveness of stem cell-based therapies and the possible complications. Patients, their family members, doctors and other experts are interviewed for their perspective and knowledge of the issue. This is where the trouble begins.

Ms. Nguyen and Ms. Bogert are not the first people who complained about their words being taken out of context to apparently support a reporter's biased conclusion. Dr. Susan Perlman of UCLA faced a similar situation when she was interviewed and quoted in a Business Week article in February 2007. I do not know Ms. Nguyen and Ms. Bogert personally, but I have no doubt that they are honest people and loving parents. Dr. Perlman is Richard's doctor, I trust her implicitly. As far as I am concerned, none of these three women would lie about their views being misrepresented.

I don't know why journalists would deliberately violate their integrity in order to conform to a popular or more socially acceptable point of view. Just look at the majority of articles we've linked on our blog - the consensus is by far more pessimistic than not. Is it a case of schadenfreude in suggesting that the Chinese are failing, thus justifying the collective foot-dragging of the Western world in developing stem cell treatments or even researching the therapeutic possibilities? In the meantime, this type of negative press further polarizes the proponents and opponents of stem cell treatment. Current press coverage leads the proponents to believe that any progress will always be sabotaged by the opponents.

I am not one to subscribe to conspiracy theories nor am I willing to be mired in the emotional Strum und Draug that clouds this issue. We went to Shenzhen with the understanding that there was no promise or guarantee that the treatment would be effective. We went anyway because if we didn't try, we'll never find out. Has the treatment worked? Only time will tell. Even if it wasn't effective for Richard does not mean that it wouldn't help others. In the end it is up to each of us to decide what is right regardless of what others tell you or what you've read.

Article in today's Wall Street Journal

2007-07-02T12:51:00.001-07:00

Just a quick post --- there's an interesting article in today's Wall Street Journal about Chinese Stem Cell Therapy. More specifically, it features the Shenzhen Nanshan Hospital, Beike and ex-Nanshan patients.

Unfortunately, the WSJ is one of those publications that requires a paid subscription in order to peruse its content. I cannot therefore post a direct link to the article. Nevertheless, for those who subscribe to the Journal either electronically and/or in paper format, the title to the article is "Seeking Hope in Chinese Stem Cells" and it is written by Nicholas Zamiska. It appears in Section B page 1.

What makes the story even more poignant is the fact the patients featured are children from California. Richard worked for 20 years in Cupertino where the Nguyen family hails from.

Second Month Progress Report

2007-06-21T12:51:00.000-07:00

Haven't posted for a while. We've been back for over two months now. There's not much change, for better or worse. Aside for the sprained ankle, we've noticed that Richard has a few minor setbacks in choking, manual dexterity and energy level. Perhaps Richard will ask his doctor to increase the dosage of Prozac to control the choking. The power web OT finger exerciser is on order and will be arriving soon. In terms of energy, Richard is resuming his Creatine powder drinks that he had let lapsed after we came back from China.

On a positive note, Richard is doing better at our weekly Pilates class. He's not huffing and puffing. Also his walks on the treadmill are steadier, faster and longer. He continues to go to the Y and uses his recumbent bike to maintain strength in his limbs. Lately, he's taken to wearing an eye patch over one eye while riding in the car to lessen his double vision. I can't help but laugh every time I glance at my rear view mirror and see this pirate in my car.

It is hard to keep up with the daily exercise regimen at home. I think that's why staying at Nanshan produced better results. At the hospital, Richard is removed from the conveniences and luxuries of home so that his main focus is his daily PT and OT. Once back home, there are the cable TV, the internet, books, magazines and newspapers, not to mention a soft, comfortable easy chair to tempt him into taking it easy.

Our friend and fellow Nanshan Ataxian, Nick, recently sent us an interesting link about a man who gave a presentation at this year's NAF (National Ataxia Foundation) conference about his unique system of training someone with Ataxia to walk unassisted:

http://www.walkingwithataxia.com/

Richard is in the process of checking it out. It would be great if it works. Thanks, Nick!

There are two annual events that we plan on attending. They are:

ACARM (All California Ataxia Research Meeting) held at Irvine, CA on October 14, 2007

http://home.comcast.net/~fernandesml/ACARM6.pdf

and the NAF Annual Membership Meeting held at Las Vegas, NV on March 28 - 30, 2008

http://www.ataxia.org/pdf/2008AMMDestinationInformation.pdf

Our stem cell class at Stanford starts next Monday. I have yet to do the first assignment which is to read the first chapter of the lecturer's, Christopher Thomas Scott, book. Richard and I are looking forward to learning more about the subject. It is a good thing that there's so much progress made and yet for the afflicted, it doesn't seem to happen fast enough.

Exercise Redux and other ramblings

2007-06-10T16:25:00.001-07:00

Here is a quick update as to the goings on ....

the ankle has been steadily improving. I'd say that it is about 95% of where it was.

we now have a treadmill at home so that instead of pacing up and down the hall, I can exercise while being in one place.

after a recent physical examination, my GP also added his support for future prospects for stem cell treatment.

I realize how much bio-technology has advanced over the years.. I am reminded of an incident several years ago where I had to attend a remedial traffic school session. It was held at a local middle school's science classroom on the weekend (~ 8th grade). During one class break, I pondered at some of the posters on the bulletin board. The subject of the poster: DNA.

I attended college in the late '70s (not majoring in any biotechnology related discipline) and had attended the 8th grade in the early '70s. Suffice it to say that DNA was never even mentioned in the textbooks and was the subject of cutting edge research. I only have to imagine where topics such as RNAi, stem cells, nuclear transfer, blastocyst, etc. were mentioned in closed laboratory offices and technical conferences.

Potpourri

2007-05-29T16:37:00.000-07:00

Richard's ankle is finally healing and he's easing himself back into his exercise routine. His Pilates session last Thursday produced profuse sweating and an alarmingly pale face that I have not seen since his first stem cell injection more than two months ago. It is sobering to realize how quickly the body atrophies. On a more positive note, Richard has found that he no longer has to use to the bathroom at night since returning from China.

One of the many symptoms of MJD is frequent nocturnal urination. A few days before we were scheduled to leave Nanshan, Richard woke up in the morning and realized that he slept through the night without having to use the bathroom. He was cautiously optimistic at first, fearing that it was a fluke. For the past month, unless he drinks copious amounts of coffee after dinner, he seldom finds himself waking in the middle of the night to visit the bathroom.

We finally bought a treadmill which will be delivered and installed tomorrow. Together with the recumbent bicycle and hand weights, Richard will have a fairly complete set up for his PT. I've located an online vendor that sells parallel bars and OT supplies. Those will be next. Richard's manual dexterity has started to worsen a bit so I need to get him to do the OT exercises.

We will be attending a seminar given by the Stanford Institute for Stem Cell Biology and Regenerative Medicine on "Harnessing the Power of Stem Cells" tomorrow evening. The keynote speaker is Dr. Irving L. Weissman, the director of the Institute and co-founder of biotech company, StemCells, Inc. There will be two other lectures that evening on "Embryonic Stem Cells" and "The role of stem cell treatment in the repair of the brain and its functions".

Furthermore, thanks to our friend, Cathy, who pointed out the course to us, we've enrolled in the course "Straight Talk about Stems Cells" at the Stanford Continuing Studies Program. Here's a link to the course description:

https://continuingstudies.stanford.edu/course/BIO53.asp

Our objective is to keep abreast of the latest development in stem cell treatment in the United States in the hopes that it will be available in the U.S. in the very near future.

Speaking of stem cell treatments, our friend Fabio emailed us two interesting links recently. Fabio's mother, Nadja, has ALS and was treated at Nanshan the same time we were there. The following links are of facilities offering stem cell treatments in Cologne, Germany and the Ukraine respectively:

http://xcell-center.propreventa.net/index.php?id=|&L=1

http://www.emcell.com/

Breakpoint

2007-05-17T22:25:00.000-07:00

I was first introduced to the book "Breakpoint" by Richard A. Clarke while resting in my Nanshan Hospital room after a lumbar punch. It was an audio book that I downloaded from Apple's iTunes. It touches on so many of the issues pertaining to my recent trip to China and my own experiences at home:

stem cell therapy
China's emergence as a world power
the World Wide Web
Cambridge, Massachusetts

two of its major universities,
the Charles Hotel in Cambridge

the Googleplex in Mountain View, CA
bionic parents and techno-children (see link below)

http://www.salon.com/mwt/feature/2007/05/09/everything_conceivable/?source=newsletter

Now for my 2 cents.... what are the ethics concerning stem cell therapy? Should it be restricted to correcting nature's defects and/or injury or could it be used to enhance our lives? How will stem cell therapy affect the natural evolution process? Is there a gray area?

Is stem cell therapy just for the wealthy? How else does the cost and knowledge come?
Here is my opinion regarding the first question.

What are the ethics for stem cell therapy?

To the extent that we understand what is "wrong", correcting the disease or injury is reasonable. For example, restoring a person's health after paralysis due to spinal cord injury seems reasonable. I would include correcting for a known defect. This doesn't deal with the matter of testing for potential "defects" which is a volatile question in and by itself.
Enhancing the genetic makeup without a known "deficiency" seems wrong. As depicted in the book, designer babies where one buys features like shopping for a car caters to the wealthy.
Is there a gray area? Taking advantage of an opportunity to apply the latest and greatest technology falls in this category. To imagine what I'm referring to, think of The Six Million Dollar Man . Also, NBC's Fall 2007 TV lineup includes the Bionic Woman.

Take a look at the book or listen to the audio version. I highly recommend it.

Is stem cell therapy just for the wealthy?

How else does the cost come down and the experience come about? There seem to be very few organizations willing to foot the bill. Even the "wealthy", as individuals, cannot sustain such an effort on a broad front. The primary thrust needs to come from the support of governments which are among the few institutions large enough to support such an effort.

A note on my progress. After returning from LA, I re-sprained my left ankle, The good news is that it isn't broken or fractured. The bad news is that I restarted the healing time after two and a half weeks and the ankle is still a little swollen.

Signs and Wonders

2007-05-09T22:43:00.000-07:00

We just got back from Los Angeles and our visit with Dr. Perlman at UCLA. After a thorough examination, Dr. Perlman determined that Richard has a 3 point improvement in his SARA (Scale for the Assessment & Rating of Ataxia) score which demonstrated a measurable difference in his condition post-stem cell treatment.

As we understand it, the SARA scale ranges from 0 to 40 with 40 being the worst possible ataxia score. Just prior to our China trip in early March 2007, Richard's score was around 16 or 17. His score this past Monday was about 14. Of the eight areas (gait, stance, sitting, speech, finger chase, finger-nose test, fast alternating hand movements, and heel-shin slide) that SARA measure, Richard showed improvements in gait, stance, alternating hand movements and heel-shin slide. Richard demonstrated that he can now stand upright without support for an extended period of time. His gait while ambulating on his walker was much steadier. When asked to walk while holding unto my arms, he surprised me by only placing his hands lightly on my arms. In previous times, his grip was vice-like. His alternating hand movements appeared to be smoother as was his heel-shin slide.

We are very encouraged by these quantifiable improvements and believe that Richard will continue to do better as his ankle is almost all healed and he can resume his exercises at home and at the gym. Our daughter, Andrea, has just finished her year at college and flew back home with us today. We hope that with Andrea's, my and Jovie's (Richard's new CNA) assistance, Richard will be able to get enough PT and OT workouts most days of the week. Jovie is a great asset since he is quite familiar with PT exercises and is able to make suggestions to Richard while accompanying Richard to the gym at the Y.

Top Ten Reasons Why I'm Glad To Be Home From Nanshan Hospital

2007-05-02T11:35:00.000-07:00

Food is available in a wider choice than Chinese food, KFC, McDonald's, or pizza
Folks address you in a language you understand
You can sleep in without worrying about the hospital staff awakening you
You can cross the street without getting run over
People will hold open the elevator for you
I can see the sun a lot more
You can use your credit card to buy something without worrying, "Am I carrying enough cash?"
Web sites are all accessible
You don't have to decide which side of your body to insert the needle

And finally ...

Nothing else compares with the comfort of your own bed, pillow, and blanket

I made my second trip to the YMCA the other day. Unlike the prior week, my muscles weren't quivering. As Lily had mentioned, I just wish I hadn't sprained my ankle and that this insomnia would go away.

May Day

2007-05-01T23:31:00.000-07:00

We've been back for two weeks now. There's not much progress to report. Jet lag is the most formidable obstacle in our "recovery" process while our friends and family are the best facilitators. Unfortunately, Richard sprained his ankle a few days ago. Despite ice packs and elevating the foot, it is still visibly swollen and bruised. I suspect that it'll take some time to heal.

In terms of PT and OT, Richard has gone back to the local Y for his regular weight training on the different machines. As he has written in his previous post, it has been tough going. His energy level and stamina is good but not as good as when he was in Shenzhen. We attribute this to jet lag and the lack of the rigorous Nanshan PT regime. There is no OT at the moment because we're still looking for the tools needed to replicate Dr. Ye's exercises.

Jet lag has hit Richard much harder than it has hit me. He has been sleeping very badly at night and often does not drift off until dawn. He then sleeps until late morning. In a last ditch effort, he decided to take Ambien at bedtime in an attempt to reset his body clock. It has worked well the last two nights. However, on the first night, he had night terrors that woke me up. As usual with his night terrors, he did not recall the details of his dreams. However he said that it is proof enough that he is getting to the REM stage of sleep that is restorative. I will keep a close eye on his Ambien intake to make sure that it does not become a regular habit.

Today is May Day which marks the start of the Golden Week, the annual seven day national holiday in China. My thoughts wander to Nanshan and the patients on the Stem Cell Ward. It will be trying for them this coming week since the hospital will be operating with a skeleton crew. Restaurants, shops and tourist attractions will be similarly affected, but I'm sure that the Beike staff will make sure that everything is taken care of.

We head to LA this Saturday for Richard's check up with Dr. Perlman at UCLA on the following Monday. It will be interesting to see what the check up reveals.

Exercise is the yuppie version of bulimia

2007-04-25T11:01:00.000-07:00

The title is from a book titled Food Worship. Being born in the late '50s, I would call myself a late Baby Boomer. Growing up in New York and attending college in the east, I've seen my share of Yuppies.

I physically don't enjoy the act of exercising. I don't mind what I do to pass the time but that is not the motive itself. I do it both out of necessity as well as liking the results.

Before Shenzhen, I would visit the YMCA once or twice a week, do Pilates with Lily once a week, and go on an exercise bike at home on the other days of the week. The emphasis would be "balance neutral" activities.

Since our trip to Asia, the emphasis shifted to sustaining and enhancing the skills taught by the various therapists to put the stem cells to use. Exercises taught and practiced in China would be duplicated if possible. Easiest among these was adding some weights for arm exercises. Not losing the strength I had before is another story.

Yesterday was my first visit to the local YMCA since returning. I wasn't so much panting as certain muscles were quivering near the end of the repetitions. Muscles that were used to 70 pounds two months ago were trembling at the same settings.

It has become apparent that after just a month of disuse, muscles can very easily atrophy. Avoiding injury has a renewed importance. I can't wait to see how Pilates goes at the end of the week.

I wish I had an answer to that, because I'm tired of answering that question

2007-04-23T12:52:00.000-07:00

The title is another Yogi Berra-ism. The question I am referring to of course is, 'Have I noticed any improvement?" I did not mean to be cynical in my response to this question. Everyone asking has been sincerely wishing me good luck. I just thought it was an amusing quote.

For those who don't know who Yogi Berra is, he is a former NY Yankee baseball catcher in the late '40s and '50s and manager in the '60s. See http://www.yogiberra.com/yogi-isms.html for his web site and some of his other quotes.

The answer is yes, I have noticed change, mostly improvement. I attribute this to both the intensive therapy and the stem cells. The way I think of it, most tasks require a combination of strength and control. Muscles can easily atrophy from disuse thus losing their strength. Therapy and acupuncture help restore this. Control is via the brain. The fresh stem cells are intended to rejuvenate this. Without both, neither effort alone isn't brought to its maximum benefit.

Some of the specifics in my case are as follows. I've updated this web site with a final handwriting sample (see below). While folks' comments have ranged from the samples look "comparable" to "some improvement" to "noticeable improvement", I can say that my writing is tighter and more controlled, and my hand cramps less. The former would be due to stem cells while the latter I would attribute to therapy (i.e. hand strengthening exercises and hand massage).

Another example is upright walking. I still use a walker. However, I have a narrower gait and I look straight ahead more so (rather than down at my feet). I always had the strength to do the walking. I think the stem cells helped improved the control. However, many of the physical therapy exercises were geared to reteaching the brain what had been forgotten after years of disuse.

I plan to revisit both my local neurologist and Dr. Perlman @UCLA within the next two weeks for an "after" picture. Hopefully, I can present a less subjective view after these appointments.

On a separate note, many friends have wanted to welcome us back home, often by offering to eat out together. With doctor's appointments and jet lag, our availability has been somewhat limited in the past week. We wanted to thank everyone for their well wishes and kind gestures and look forward to getting together and thanking you personally soon.

Life in the slow lane

2007-04-18T22:31:00.000-07:00

Home at last! Our stay in Hong Kong was restorative in every sense --- family, food and rest. Delectable food, feather-soft beds, showers so bracing that the water literally excoriates dirt off the skin and coddling from Mom made up for a month's worth of boot camp. Oh, did I mention shopping? However, there's no place like home. We missed the clear blue skies, the mild dry weather and the refreshing clean air. Our lungs thank us!

Today is devoted to sorting through a month's worth of mail and recent emails, shopping for groceries, unpacking, doing laundry and battling jet lag. This left no time for Richard to resume his rehab. He has used the exercise center at the hotel in Hong Kong once or twice but it paled in comparison to the twice daily PT & OT regime at Nanshan. Our goal is to have him ramp back up to an hour of exercise per day. Aside from the recumbent bicycle, workouts at the Y and weekly Pilates, we plan on purchasing a treadmill and using it as per the recommendations of Big Dr. Lee. Also, I'll be looking for pegboards and the nut and screw board that Dr. Ye used on Richard during OT. These are possibly available at teaching supplies store. Acupuncture and throat collar will be impossible to replicate here. Although our friends Jeanne and Cathy have recommended a good local acupuncturist that we may try out in the future.

We will try to post updates on this blog to avoid the dreaded silence that so often occurs when the patient returns home after the stem cell treatment. Richard is slated for a visit with Dr. Perlman at UCLA at the beginning of May. We will be certain to post her comments and any findings of the visit.

*Speaking of posts, the photos of the "So long and thanks for all the fish" post are up again and this time they are captioned.

Bon Voyage - The Return Home

2007-04-15T19:26:00.000-07:00

It's Monday morning here in Hong Kong. It's our last full day here in Asia. I'm in the hotel lobby banging away at the keyboard, checking e-mail, etc. I've cleared out of the room so that it can be cleaned up.

I just went on the exercise bike in the "fitness area" for about 20 minutes. I could/should put in more exercise time but it's easy to succumb to visiting family, eating out, etc.

We've already started to hear from recent patients from the stem cell ward. The cheering on continues. Some folks have had more adventurous returns. We depart for home Tuesday evening. Fortunately, it's a non-stop flight for us and we don't have excessive luggage.

Also, a quick update. The renewed choking while eating went away when I brought the food to my mouth and stopped craning my neck. Problem understood.

So Long, and Thanks for All The Fish

2007-04-13T03:24:00.000-07:00

This entry is dedicated to our daughter, Andrea, who is a great fan of the Hitchhiker's series by Douglas Adams where the title of this entry originated.

As we wrap things up here at Nanshan, we thought that it's time for a bit of show and tell. This post will be light on text and heavy on pictures.

Nurses and Camillia (in pink). Camillia is the member of the Beike staff who exchanges your dollars for RMB/yuan.

Dr. Yang (the younger). The other Dr. Yang (the elder) is the chief neurologist.

The cleaning ladies. They have an extra set of the room keys and can help you get back into your room if you accidentally lock yourself out.

Dr. Kitty Guo (far left in stripe skirt), nurses, and Dr. Yang posing with a banner that we've presented to all the doctors, nurses and staff of the Stem Cell Ward to thank them for the excellent care that Richard has received. The woman directly behind Richard in the dark top is Lily, the head nurse. Dr. Guo is the Beike staff member who is in charge of scheduling the stem cell injections.

Big Dr. Lee, Little Dr. Lee, Dr. Wang, Dr. Shu and Dr. Ye with the banner that we've presented to Big Dr. Lee and Dr. Ye thanking them for the care they've provided to Richard.

Big Dr. Lee (PT & acupuncture) & Dr. Ye (OT) with banner.

With Dr. Ye and the collar that sends out electrical pulses to the throat.

Dr. Ye & Big Grace, the Beike program manager.

Little Grace and Cherry, the Beike staff member in charge of the PT & OT (4th) Floor.

Dora, Beike program patient manager and Jillian.

Nadia, Helen, Paola and Ylenia. Nadia & Ylenia are from Brembate, Italy. Paola is from Sardinia, Italy and Helen is from Florida.

John and Will from Thomasville, Georgia.

Ylenia and Fabio (Nadia's son) from Brembate, Italy.

Enid and her husband, Benny from Johannesberg, South Africa.

With Frank, the Ataxia patient from Hong Kong. All stem cell patients from Hong Kong and China are put on the 4th Floor of Nanshan.

The home stretch

2007-04-12T00:48:00.000-07:00

These last two days have been a whirlwind of activity. We didn't think that anyone would notice that we did not post yesterday but Ernesto did! Yesterday marked the 20th anniversary of my father's passing. My mother held a Buddhist memorial service in Hong Kong which lasted from 9am to 4pm. I went to Hong Kong in order to participate in part of the activities but hurried back just in time for Richard's 4pm LP. The procedure lasted a little longer than usual because Richard misunderstood the doctor's instructions and straightened out his back too soon during the injection. Luckily there were no complications and he had a restful night's sleep, waking up headache free.

Before going to bed last night, Richard was treated to Paola's homemade pizza. Paola is from Sardinia, Italy. She is accompanying her brother, Antonio, who has ALS (Amyotrophic Lateral Sclerosis or Lou Gehrig's Disease) to Nanshan for treatment. I got her some Italian pasta, spaghetti sauce, tomato sauce and olive bread while I was shopping for groceries at Portofino. She was overjoyed because she couldn't find any of these ingredients locally at Nanshan. Thus, she returned the favor by making Richard the delicious pizza.

Today I went with my sister and brother-in-law to visit my father and grandmother's grave sites. They were both buried in Shenzhen. Richard, on the other hand, was invited to tour a new hospital facility in Shenzhen that Beike is considering as a potential candidate. The Beike staff wanted Richard to provide them with feedback from the patient's point of view in terms of accessibility and desirability of the facilities inside this hospital. As a result, he missed the afternoon sessions of both PT and OT.

We find that time seems to zip by as we head towards the home stretch of our stay in Nanshan. We've decided to check out of the hospital early to spend time in Hong Kong for some R&R and to visit my mother. If all goes as planned, we'll be leaving Shenzhen late Saturday morning for Hong Kong. Tomorrow will be our next to last day at the hospital. We plan to put it to good use as we bid our fond farewells to the doctors, nurses, staff and patients who we've grown very close to and fond of during our time here.

P.S. We've posted a sample of Richard's handwriting after 3 weeks of treatment at Nanshan in the right hand column under "Before and After". Is there improvement? You'll be the judge.

The bells of Portofino

2007-04-10T03:26:00.000-07:00

Not too long ago, Shenzhen was a small, backwater fishing village with a relatively sparse population. When Hong Kong was still a British Crown Colony, people in China use to come to Shenzhen for a chance to enter Hong Kong illegally by swimming across the narrow body of water that separated the two cities. Many were bitten and killed by sharks that infested this area or drowned by the rip tides.

Nowadays, this ex-Tijuana of the East has become one of the major centers of China's high tech industries, attracting overseas Chinese from America and Canada and expats of all nationalities who make their homes here. Most of these foreign newcomers live in Shekou (Snake's mouth) which is just 15 minutes from Nanshan. For the prodigal sons and daughters of China returning from America, Canada and Taiwan, there is the Disneysque OCT (Overseas Chinese Town) in Shekou. Inside OCT is a small oasis called Portofino. It is a prestigious, gated community of homes, shops, cafes and restaurants built to resemble Portofino, Italy. There is even a miniature lake in the middle of the complex. By the lake is the town square complete with its own bell tower whose ear-splitting bell strikes every hour on the hour. Quasimodo would feel quite at home here.

Last Sunday evening, Richard and I decided to "go on a date" at the Portofino. We arrived in the late afternoon and strolled around. We bought freshly baked croissants and French jam for breakfast and foccacia bread, Barilla pasta and tomato sauce for dinner the next day. The entire complex was fully handicap-accessible with ramps everywhere. This is the first time that we've seen ADA facilities in Shenzhen. However, some shops and restaurants still have steps and thresholds that are challenging for the mobility-impaired. We spent the rest of the evening dining al fresco at an excellent restaurant with a view of the lake. It is amazing what a nice evening out can do for the soul.

My sister, brother-in-law, Aunt Lucy, Uncle Robert and cousin Mei Ling all came to visit us today. We're very lucky to have relatives locally. My sister and brother-in-law are visiting from Toronto, Canada and we were overjoyed to see them since it has been some time that we've seen them last. We are eagerly waiting for Richard's last stem cell injection by LP tomorrow. Wish him luck!

Top Ten Reasons You Know It Is Time to Go Home

2007-04-09T03:52:00.000-07:00

When You Look Like Your Passport Photo, It's Time To Go Home - Erma Bombeck

You consider discharging goods you bought a few weeks back because of concerns of excess luggage

The delivery boy from Papa John's Pizza is on a first name basis with you

You are bored of KFC and McDonald's

You act out all your PT and OT exercises in your dreams

The person on the restaurant takeout phone says, "Oh, it's you again."

The following quote makes sense: "Healing is 90% attitude, 90% medication"
[ I had to insert this bit of Yogi Berra-ism ]

You know your way around Lo Wu City shopping center

The street vendors recognize you and refuse to bargain with you

You are greeted in every language except English

It was extra busy at PT and OT today because the interns have just finished their training and the doctors are left to tend to all the patients by themselves. Godzilla (the construction machinery) is again screeching for her young.

We had an interesting encounter in OT. We met a Chinese ataxia patient who is being treated with stem cells on a different floor. He is from Hong Kong and has SCA6. He says that there are about 100 known ataxia patients in Hong Kong. As we find out more information, we'll post it.

We're on the home stretch now. I'm feeling energetic enough to use my walker within the hospital building. In the evening, as I walked on the floor I heard one of the Italian patients called, "Bravo Ricardo!!" Subtle signs of improvement have been noticed.

The Caregiver

2007-04-08T00:41:00.000-07:00

Usually a family member or close relative or friend, the caregiver will assist you with the basic needs that might arise. This is especially true for companionship. Depending upon who this person is, he or she may also act as the patient's advocate. She has the additional objective of looking out for the patient's interests during and after the treatment.

A true luxury is when the same person remains for the entire stay, normally a month. Very often, the patient will be escorted to/from Shenzhen but will have to hire a local caregiver. The disruption in work and vacation time for the caregiver may be excessive.

There also is the act of being away from friends and other familiar surroundings for an extended period. Living out of a suitcase, determining where your next meal will come from are all hardships. The disruption of "living conditions" is traumatic; after all, since when is a hospital setting the first choice for lodging? Also, Shenzhen is a very dense urban environment. There is only a fraction of the population that is comfortable in those surroundings.

Now add the ever present "foreign tongue". There are only several Asian countries that would be considered fluent in the Mandarin dialect.

I have been very, very fortunate. My wife, Lily, has performed so many of the above tasks flawlessly and I've benefited from a top notch advocate. We visited with local relatives and expect to see more in the coming days. However, dislocation from friends and familiar surroundings have taken its toll. We are anxiously awaiting our return home.

Friday was my fourth of five stem cell injections. No headaches and all is progressing without any complications from this latest lumbar puncture. The rash mentioned in an earlier posting has subsided. The last stem cell injection is due Wednesday.

We've noticed a little bit more choking/gagging during meal times. I think we correlated this with eating in the hospital room. Since unlike home, I cannot wheel up to the table in my wheelchair, I either have to crane my neck (and risk a gag reflex) or risk some spillage by bringing my food over my lap to my mouth (without craning my neck). In restaurants, I don't seem to choke because I can wheel up to the table. I'll mention my findings in one of my next posts.

Days of our lives

2007-04-07T08:13:00.000-07:00

Our friend and neighbor, Jane Ellen, once jokingly referred to this blog as her daily dose of "Reality Show". Little did she know how right she was. The comings and goings of the residents of 14th Floor Taoyuan Road rival those of the denizens at Melrose Place. There is courtship between the young nurse and her patient's son that eventually fizzled out. Then there is Lady Machiavelli who so skillfully manipulated me that I fell into her trap willingly. But in general, the folks here are kind, decent people caught in the same predicament of watching their loved ones suffer from some incurable disease and are doing the best they can to get along with each other.

There is much camaraderie amongst us. We check-in with each other on a daily basis. If we find someone missing at the PT sessions, we make it a point to verify that he/she is well. We also cheer each other on and celebrate even the smallest moments of triumph when someone is able to gain feeling in her finger for the first time in ten years. We share the highest of highs and the lowest of lows. With so many nationalities and close living quarters it is a small miracle that we all get along so well. United Nations can certainly learn something from us.

However, not all patients and their caregivers participate in this commune. Some are more reserved in nature and prefer to keep to themselves. We find that the language barrier can be daunting to many, this is especially true for the Italian and Eastern European patients. Then of course, there is the occasional oddity in the form of Mr. Body Beautiful who I've described in my post "The naked man on the floor". He almost never left his room at all during his entire stay here.

Because our weekdays are full with rehab and injections, the only chance that we get to go out either by ourselves or in a group is on the weekend. We've ventured out with a group to Sea World and had a nice, leisurely dinner at a fantastic Italian restaurant one evening. Then there were short shopping trips locally for groceries and to Lowu Commercial City for souvenirs. Most weekday evenings we while away our time surfing the net, posting to the blog or catching one of the movies that we've brought with us.

Some evenings we have impromptu going-away pizza parties in the common room. We make a toast (with Coke) to the ones who are leaving and exchange addresses and phone numbers with promises to stay in touch. We've missed Debbie and Sue from Canada who are the most fun and down-to-earth people we know, David and Karen from Scotland, and Nick and Maria from Buffalo, NY. It is generally a good idea to try to get to know the people on the floor. Aside from providing moral support, the ones who have been there for a while are invaluable resources as you try to figure out the protocol of the program.

Richard continues to do well. The bruise on his hand and the rash on his body have resolved themselves. He has started to ambulate around the floor with his walker. The most noticeable improvement so far is his stamina and energy level. He is now able to shorten his naps and stay up a lot longer. The evening that we went for dinner at the Italian restaurant, we did not get back to the hospital until past 11:30pm. At home, he is usually in bed by 10pm. His gait and upper body stability are also good. We continue to be hopeful for further improvements.

The Impeach Box

2007-04-05T23:15:00.000-07:00

By the bank of elevators on the Stem Cell floor is an inconspicuous metal box affixed to the wall. The English words “Impeach Box” appear in bright orange letters on it. Below these letters are the Chinese characters for “Complaints Box”. “Chinglish” signs can be found everywhere both inside and outside the hospital. Some are side-splittingly funny while others are just plain mystifying. My favorite so far is the phrase “tenderly reminding” which prefaces every bulletin and warning posted in the corridors and elevators. We are hereby lovingly and gently reminded that there is no smoking in the waiting areas and that certain exits will be inaccessible after certain hours.

Speaking about the Impeach Box, I would like to submit the following item for consideration:

Yesterday afternoon while Richard and I were at PT, I received a sharp rap on the top of my head by Dr. X (to protect his privacy, he will be unnamed), a PT doctor/therapist, who then upbraided me for sitting on the a piece of rehab equipment. I was in a state of shock because in the entire three weeks that we’ve been in PT, Dr. X has never spoken to me, save once. A week or two ago he told me that I could not park Richard’s wheelchair in the PT room. My cousin from Shanghai was visiting us at the hospital then. My cousin was the one who put the wheelchair there because she was not aware of the rules. Nevertheless, I apologized to Dr. X and brought the chair out.

Going back to the rap on my head, I reacted by jumping off the rehab equipment that I was sitting on (it was a padded bed with a U-shaped indentation at the head of the bed). Apparently, I was being reprimanded for sitting on the head of the bed. Richard has never used this piece of apparatus before for his PT. There were no signs or warnings posted in either Chinese or English on the equipment. It was not intuitively obviously, at least to me, that the head of the bed was fragile. The knock on my head was not painful but it had enough impact to be jarring both mentally and physically. I was embarrassed to be treated like a naughty child in front of all the patients, their caregivers and other therapists.

As the day progressed, I could sense a feeling of unease welling up inside of me. But I couldn't put my finger on why I was feeling that way. Later that night, I lay in bed running the day’s events through my mind. Was Dr. X’s rap on the head a Draconian punishment? More fundamental that that, what excuse does he have to meter out punishment to me, a stranger? Does he even have the right to even touch my head without asking? Could a similar incident happen in the United States or any other parts of the world? Yes, no, no and probably no in other parts of the world.

Because I could not think of a single occasion that I have offended Dr. X, it is baffling to me that this person should resort to physical force to get my attention. The only explanation that I could come up with is that I was the chosen victim or some scapegoat for their discontent. I did not come 7,000 miles to be someone’s punching bag. This thought so disturbed me that I had a sleepless night.

This morning, I spoke to Grace and Dora, the Beike program and patient managers at Nanshan. They were sympathetic and promised me that they’ll investigate the matter. I had two objectives in reporting this incident. First, I want to bring to their attention that such behavior is totally inappropriate and unacceptable. Even if it is condoned in China, which I doubt, I will not tolerate it. Secondly, I told them that if Dr. X were ever to behave inappropriately towards me again, I will take my compliant to a higher level.

A short while after, Dora came to my room and told me that she and Grace have had a chat with Dr. X. He was surprised that I had taken such offense to his “playful trick”. Furthermore, Dr. X had misinterpreted my rueful smile after receiving the rap on the head to be a smile of pleasure. Dora explained that Dr. X was totally caught off-guard by my complaint. Dr. X thought that I understood that he was just being “playful”.

I can see how I might have blown the whole incident off as high jinx had it been big Dr. Lee or the other doctors/therapists who had administered the blow. Over the last three weeks, I have chatted up all the doctors/therapists in both the PT and OT areas but Dr. X. Beyond the quick nod or “good morning” now and then, I have never elicited any conversation from Dr. X before. It therefore makes no sense that he would consider himself acquainted enough to “play a trick” on me.

For now, I will give him the benefit of the doubt. In the meantime, this unfortunate incident was the straw that broke the camel’s back. More than ever, I yearn for my family and friends, for their soothing words and touch, for their skill in coaxing me out of my melancholy. I am exhausted and demoralized. I remind myself that there is only another week left and it can’t come too soon.

Beginning yesterday, Richard has developed a mysterious rash on his upper torso and buttocks. Although the rash is somewhat noticeable, it is neither itchy nor painful nor does he have a fever. The two Dr. Yangs wanted Richard to be seen by a dermatologist at the outpatient clinic. This poor dermatologist was dispatched three times yesterday afternoon to come up to our room for a consult and all three times we were out at PT or OT or on our way up to the room.

We finally saw the dermatologist today and she confirmed that it was nothing more alarming than some sort of contact dermatitis resulting from either the recent changes in weather or the new detergent that the laundry company was using. (We have been sending our laundry out to be washed since the humid weather makes it impossible to air-dry clothing) She prescribed some skin ointment and oral medication. Richard is now resting comfortably on his bed waiting for the stem cells to arrive for his third lumbar puncture at 4pm.

Food glorious food - but beware

2007-04-05T06:29:00.000-07:00

China is very much a developed country, with some caveats. Specifically, one should be cautious with foods. The following advice comes from my own experiences in China and Hong Kong:

One should expect packaged and bottled goods to be fine. I would avoid street vendors, but most established sit-down restaurants are fine. Also, delivered cooked foods are fine, but raw fruits and vegetables must be washed thoroughly. I would avoid the skins of most fruits. Salads are not widely served, perhaps for a reason.

Tap water is fine for gargling such as when you brush your teeth. However, I would only drink boiled water or bottled beverages. Beware of iced drinks since the ice cubes may be made from tap water.

There are some special rules for seafood. I would avoid uncooked shellfish and probably uncooked fish in general (i.e. sushi). Cooked seafood I would consume but in limited quantities.

End of my sermonizing.

Godzilla hasn't called the last two mornings so we've been able to sleep in a little more. Godzilla is our nickname for the construction machinery. We met son of Godzilla in the freight elevator the other day in the form of a rusted trolley. The screeching sound was spine tingling.

Today was a little different in the hospital. The morning routine includes Acupuncture and Physical Therapy. Dr. Lee suggested that instead of using a wheelchair within the hospital, I need to get up and use my walker. Morning PT was also delayed as I've developed a non-itchy rash. I hope I didn't upset the dermatologist when I failed to be in my room when she came by. I'll trek over there tomorrow (Friday) morning probably.

Lunch was interesting as Lily and I went to dim sum with several key Beike staff members, Dr. Hu, Jon, and Grace. We were originally to go with two other patients and their caregivers but due to a mix up, they had to cancel last minute.

The conversation over lunch focused on how to "get out the message" that stem cells are real and are available. I now have a sense why Beike has been successful in Canada, Italy, Romania and Hungary but not as widely represented (though by no means zero) in the rest of the world.

Hope

2007-04-03T22:56:00.000-07:00

I was intrigued by the comments made by a patient in this ward. There are so many differences in the patients here: language, culture, nationality, injury/disease type, etc. The common thread though is hope. Everyone has refused to accept the response, "There is nothing more that can be done." It is one thing to be trapped in a dark room and another to look for the light that will guide you to the exit.

Today is a typical weekday in the hospital. The morning routine includes Acupuncture and Physical Therapy with PT and OT in the afternoon. The hospital staff is hoping for some visible progress as proof of the effectiveness of my treatment (like unassisted upright walking). The intangibles resulting from the stem cell therapy and rehab are better energy level and more control of my upper body.

Over the Hump Day

2007-04-03T00:02:00.000-07:00

We're roughly at the half way point of our stay and no longer seem to be the strangers among the patients. Moreover, we are envious of those who are leaving before us. We're longing for a meal at our favorite restaurant, the sight of friends and family ... in short, we're missing home!

Health wise, I'm feeling fine. I'm very glad that Monday's stem cells for me was via IV. Gone were the restrictions of bed rest and no food for six hours after the lumbar punch. This was especially crucial given that stem cells didn't arrive until 8 PM that night.

My next stem cells (fourth of five) are scheduled for Friday via lumbar puncture. So far, I would guess that my energy level is better and my upper body seems steadier. During PT, I need to retrain my brain on how to walk with a regular gait.

I think it is wise to always check with the medical staff often to ensure that one's stem cell injections happen when promised and are of the desired type (IV, lumbar puncture, etc). Give about a week before the last injections in case any changes are required; you never know if there might be unannounced changes.

I also added a link to the Google Earth community on the post "You Can Run But You Can't Hide". To use the facility, you do not have to register with Google (thanks to the suggestionof an anonymous comment). Zooming around the earth on a flying tour is pretty cool.

Have you eaten yet?

2007-04-02T00:13:00.000-07:00

With a population of over 1.3 billion people, it is little wonder that there's such significance placed on food in China. One of the most common greetings among the Cantonese is "Have you eaten yet?" In fact, the Cantonese are known to be the most finicky of gourmets whose insatiable quest for the freshest and most exotic of dishes earned them the reputation of "eating everything that has four legs except a table and everything that flies except an airplane."

It is therefore the ultimate irony that I cannot find a decent Cantonese restaurant around Nanshan Hospital. Not only are restaurants specializing in the local cuisine far and in between but the variety of the dishes on the menu dismal and inadequate. By contrast, there are Szechuan restaurants, Mongolian restaurants, Shanghainese restaurants, Peking restaurants, Shandong restaurants galore. I was told that it is because Nanshan has a large migrant labor population so the restaurants tend to cater to non-Cantonese palates.

Since arriving at the hospital, we've been ordering out our meals. There is a communal kitchen but the logistics of shopping daily for food and preparing it in an unfamiliar kitchen proved too daunting. We've found that by sticking with Chinese food, our per diem (lunch and dinner for two) amounted to no more than 70 to 80 Yuan (US$10) which is unbelievably inexpensive. Lunch is usually a plate lunch of rice or noodles, meat, and vegetables. This usually costs around 10 to 12 Yuan (US$1.50). Another of our lunch favorites is jook (Chinese porridge or congee) favored with chicken or fish. This is augmented by Deep Fried Devils (Chinese crullers) and a plate of fresh greens seasoned with oyster sauce. Dinner is a bit more elaborate. I usually order the soup of the day, a meat and vegetable dish, a tofu dish, and white rice. Sometimes, we order from the beef noodle place. The meals there come with small side dishes like tea marinated eggs, and preserved bean curd.

For a change of pace, we ordered a pizza from Papa John's last Friday. We usually see 3 to 4 empty Papa John's pizza boxes in the kitchen trash here everyday. So Papa John's is very popular at the Stem Cell Ward. Imagine our surprise when we found that a 14 inch pizza ran 100 Yuan! (US$13) By U.S. standards, the price is not outrageous, but for the locals, the same amount of money will buy a nice dinner for 8 people.

For non-Chinese speaking and reading patients, there are three alternatives in feeding themselves :

1. Shop for food at the local supermarkets and prepare the meals in the communal kitchen.

2. Go out to local restaurants (including the restaurant on the first floor of the hospital) and order from the menu which may or may not be in English. Western fast food outlets like McDonald's and KFC also have a big local presence.

3. Order from Papa John's or the restaurant on the first floor of the hospital and have the food delivered to your room.

I have a bone to pick with regards to the restaurant on the first floor. The first time we tried eating at the place, we had a fairly good experience. The food and service were OK if not memorable. The second time we went there, we sat at the table for half an hour. The staff ignored us, never bringing us even a glass of water or the menu. Needless to say, we left without eating.

Today, the heavens opened up just as we returned from Richard's morning acupuncture and PT session. I decided to give the first floor restaurant another try and ordered some food (a noodle dish for Richard and a club sandwich for me) to be delivered to our room. After an hour and a half, the food failed to appear. Every time I called the restaurant, the line was busy or the call went answered. At this point, I decided to hedge my bet and called my usual Chinese takeout place across the street. This order arrived at our room in under 25 minutes even though it was pouring rain outside.

As we were hungrily shoving down our food, there was a timid knock on the door. It was the delivery from the restaurant on the first floor. The elapsed time was slightly over 2 hours. It was almost 2pm. Our nurse happened to walk by at that moment. She told me to send the food back and not pay for it. Although I felt sorry for the delivery person I complied. Richard is having his stem cells injection by IV this afternoon. Had it been through lumbar puncture, the situation would have been serious as he would not be allowed to eat or drink after 12 noon. It would mean that he has missed his time window for lunch and would not be able to eat again until after 10pm.

The poor weather also caused the plane carrying the stem cells to be diverted from the Shenzhen airport to the nearby Guangzhou airport. Consequently, we were told by Dr. Guo moments ago that the stem cell treatment will not commence until after 8pm. We had planned on going out with another group of patients for dinner at a nice Italian restaurant but it looks like we will have to reschedule for tomorrow night.

Since I'm bilingual, (and love food) I've started to collect takeout menus from local restaurants to translate them into English so that future patients will have a choice of foods during their stay at Nanshan. I'm planning to represent this book of menus to the Beike staff before we leave.

You can run but you can't hide

2007-04-01T07:01:00.000-07:00

Thanks to our friend Peter, this weekend edition of the blog is coming to you from 22° 32' 2.26" N (latitude) and 113° 55' 8.67"E (longitude). Check out the Google Earth website if you'd like to see the actual image of the Nanshan Hospital.
http://bbs.keyhole.com/ubb/download.php?Number=628175

Today marks the occasion of Richard's first "field trip" since arriving at Shenzhen. He has been hospital-bound because of his headaches and the rather exhausting daily rehab sessions. We went out with a few other patients to Sea World this afternoon and sat outside Starbucks with our drinks, whiling away the afternoon talking and people watching. Afterwards, we went to a Tex-Mex restaurant to have an early dinner. It was a morale booster for Richard to feel like he's a part of the world again.

As usual, our presence at Sea World attracted a lot of gawking. There were three of us in wheelchairs (Richard, Debbie and Marija), Nick who walked unassisted, his wife Maria, Debbie's friend Sue, and myself. We had a heck of a time getting Richard and Marija to the bathrooms since there were numerous steps even to get into the main area of the restaurant and the facilities were not handicap accessible. But we got plenty of assistance from the restaurant staff and passersby.

When I was growing up in Hong Kong, I did not recall seeing any people in wheelchairs on the streets, shops or restaurants. I just surmised that there weren't any handicapped people living there. The only people who were visibly mobility-challenged were beggars sitting silently on the street corners. People generally ignored them or cast furtive glances their way. The infirm and handicapped were hidden away by their families to lead life as hermits. It was also the same way in China. This practice probably discouraged anyone from advocating for the rights of these individuals. Hong Kong has made great leaps and bounds in the recent years in remedying this situation while China remained the same.

In terms of the attitude towards the handicapped, I'm seeing more understanding and compassion in the majority of the people that we've come across here. When we visited Shanghai and Hangzhou about five years ago, Richard was still mobile but had to use a cane to walk. While visiting Zhou Zhuang, a tourist attraction, we had to cross numerous narrow arched stone bridges. People around us grew impatient because Richard had to walk very slowly on these bridges. They clucked their tongues, cursed, shoved and cut right in front of him making every crossing an ordeal. I cannot see the same thing happening today in Shenzhen although I have a sneaky suspicion that this courtesy is granted more frequently to foreign guests than to Richard who looked like a local.

Now and then, we still catch glimpses of the mistreatment. Yesterday, I went with Kim Poor's friend and fellow Arizonian, Marija, and her family to Lowu Commercial City to do some shopping. The place was even more of a madhouse than usual because it was the weekend. It was wall to wall people. After just a few hours, we beat a hasty retreat. As we reached the head of the taxi queue, I walked ahead to ask the taxi driver to open up the trunk so that I can put Marija's wheelchair in. The driver responded by stepping on the gas and speeding ahead to pick up another passenger at the adjacent queue. This repeated itself four different times.

Meanwhile, I'm standing amidst the gas fumes with Marija sitting flabbergasted in her wheelchair. She was trying to comfort her 4 year old daughter, Sienna, who was on her lap because the youngster was both tired and hungry. Marija's mother, Sonia, was equally exasperated . She had purchased so much stuff that she was lugging a huge suitcase filled with her purchases. When the sixth taxi finally arrived, a man and a woman jumped the queue, cut in front of us and started to open the door of our cab. This prompted spectators to cry "Yu mo gow chor!" ("You've got to be kidding!" in Cantonese) The interlopers quickly withdrew and scurried away from the angry mob. In the mean time, someone got the attention of a policeman who was standing a few yards away. It was his job to see to the orderly loading and unloading of the cabs in this area. He had observed the fiasco with great detachment so far. People started to motion impatiently for the policeman to come over to intercede.

As we hurried over to the cab, several men in our queue volunteered to assist Marija into the cab. One man spoke soothingly to Sienna in broken English to ask her to wait while I helped the cab driver load the wheelchair and suitcase into the trunk. All these good samaritans spoke Cantonese and from their accents, I'm sure they were from Hong Kong. I've never been more proud of my heritage. Richard and I have experienced similiar discrimination and mistreatment by taxi drivers in the U.S. Therefore, I'm not condemning Chinese cab drivers but all cab drivers who are too apathetic and lazy to do their jobs. I hope that there's a special place for them in hell.

Note: In an effort to encourage more comments, we've modified the blog settings to allow non-registered readers to leave their comments. We love to hear from you, we missed you all!

Dear Diary

2007-03-31T00:43:00.000-07:00

No headaches but a little tired. It's the upper body sort of tired when you exercise more than usual. I am now awaiting stem cells via IV next Monday afternoon.

The construction noise wasn't too loud this morning. It is mostly traffic sounds. At its peak, the construction noise sounds like an angry Godzilla seeking its missing child. Godzilla came back Saturday afternoon and is now calling.

PT was very quiet today. Big Dr. Lee took advantage that most patients chose to pass on PT today (Saturday). Instead I only went for acupuncture.

I had an interesting encounter at OT Friday afternoon. I was wearing a T-shirt that had the Maxwell's Equations and the phrase "and there was light" on it. For the unfamiliar, Maxwell's Equations describe electricity and magnetism in four very concise but mathematically sophisticated equations.

[ I promptly forgot these equations after finishing the final exam for the classes! ]

Back to OT ... I was sitting across from an elderly gentleman in his 70's (?) receiving some treatment. He noticed the writing on my T-shirt and asked Lily, "Is your husband a mathematician? I used to be a chemistry professor and recognized many of the same symbols." It is odd how certain concepts transcend languages.

Comments to the blog normally require registration with Google. If that bothers anyone, you can email the comments directly to us (we're still able to view our email). Let us know if you also want us to post on your behalf.

Room with a View ... Addendum

2007-03-30T02:36:00.000-07:00

After speaking with several other patients in the ward, we've discovered a couple of things about our room. It sits on the noisier side of the hospital nearer to the major street construction. It happens also to be a bit larger. Not only is there room for three beds (but assigned to one patient), but there are also drawers along the wall and separate closet space for each patient's belongings. In contrast, some rooms have accommodations for only two beds and may lack the drawers along the wall.

One other observation is that the toilet, shower and sink are not 100% wheelchair accessible. The shower is blocked by the toilet, which itself is close enough to the bathroom door to require leaving it open if you need to use a wheelchair to get in/out of the toilet. There are ample handrails along the bathroom perimeter. However, due to Kim Poor's experiences in Fall 2006, there is now rubber place matting in the shower area. Be forewarned, the matting is hard on the feet.

The sink area, located outside of the toilet, doesn't allow a wheel chair user to wheel up to the sink. One has to reach over the edge of the sink.

I know, picky, picky, picky!

So Far, So Good

2007-03-29T03:15:00.000-07:00

The second lumbar puncture/stem cell is progressing; cross your fingers that it stays that way! At least from an unscientific perspective, my energy level seems a bit better. I was cautioned though not to overtire myself. Is this the stem cells at work? Or is it the very intense physical therapy? Hard to say.

One observation I made may help others avoid the headaches from the lumbar puncture. Of course this is purely anecdotal but you never know. When the hospital administers the lumbar puncture, you are instructed to lie flat on your back for six hours WITHOUT a pillow. Your spine (at least from the shoulders up) is straight.

During the evening when we had asked a nurse for guidance to empty my bladder (I was given a portable urinal for this purpose) she suggested that I could be flipped onto my side (with a pillow supporting my back) but that I should keep my head straight as before.

I took this to mean that it is important to keep the spine from the shoulders through the neck straight. Thus as a preventative measure, I went to bed flat on my back without a pillow. I still turned my head now and then as this doesn't seem to disturb the spine. Again thus far, no headaches.

One other item Lily had mentioned in the comments section of the previous post was that a red swelling has appeared mysteriously on my hand (where the IV was placed) after I emerged from stem cell injection yesterday. There is an update to this.

This photo was taken from Wednesday evening right after the stem cell injection. Since then, the swelling has gone down and the discoloration is less severe and now it is just discolored. There was never any pain or loss of function. The consensus by Doctors Yang (senior), Guo (Beike), Lee (PT) and Ye (OT) was that this was not associated with the stem cell procedures (my knuckle was not affected and it is in between the site of the discoloration and the IV entry point). Instead, the more likely culprit is that this was a delayed reaction to an acupuncture needle that was introduced to my hand just this week. More importantly, it'll probably go away on its own as it seems to be doing.

Pray for no complications with either the lumbar puncture or the hand discoloration. The next scheduled stem cell injection is via IV next Monday afternoon.

The naked man on the floor

2007-03-27T22:12:00.000-07:00

The Stem Cell Ward is a busy place. Everyday there are patients leaving to return home and new patients coming in for the first or second time. It frequently resembles a bustling hotel.

My Aunt Lucy visited this morning. I was giving her a tour of the facilities and as we were walking by one of the rooms we heard a voice calling out rather urgently for someone to come in. Aunt Lucy, forever the good samaritan, suggested that we should investigate because she feared that the man behind the door has fallen down and was calling for help. As we gingerly opened the door, we spied a man, totally in the buff, sitting on the floor with his back towards us. After recovering from our shock, I remembered being told that this man was the bete noire of the ward. I quickly led Aunt Lucy out of the room and told her that he was not quite right in the head. Then I went to the office to alert the Beike staff. They apologized profusely and said that Mr. Au Naturel was having emotional problems and that he has had these problems even before his arrival at Nanshan. He was threatening the staff that he was not going to leave after completing his treatment. They were in the process of helping him move out of the ward and into a nearby apartment.

Aside from the price of the treatment, there are other intangible "costs" associated with coming to China. First of all, it is the cultural shock of being thrown into an environment where the climate, language, food and customs are totally jarring even to the most seasoned of travelers. I've been told many times by other patients that the Chinese food here is different from the Chinese food "back home" and that they found some of the local cuisine a bit too exotic for their tastes. In all honesty, Richard and I are doing well with ordering takeouts here, but this is because we grew up eating home cooked Chinese food.

Secondly, the length of the treatment (one month) is very wearing on both the patient and caregiver. I'm use to being able to go where I like and do what I please. Daily rituals like watering my orchids, putzing around the yard or walking to the mailbox to get the mail are gone. These things may seem mundane but they keep me grounded and provide me with a sense of order and regularity. Add to this the close quarters, jet lag, construction and traffic noise, humidity, and lack of proximity to friends and relatives and, after some time, we find ourselves thinking of home.

Lastly, it is inevitable that one suffers setbacks during the course of the treatment. For Richard, it was the initial headaches and the lack of visible improvement that were disappointing. While we understand that it is naive to expect instant results, it is human nature to hope for the best. Because some patients have other health problems that are either direct or indirect sequelae of their major affliction, e.g. poor circulation, high blood pressure, etc., they are more prone to experience unforeseen illnesses during their stay. Fevers are not uncommon. However, these are dealt with swiftly and efficiently by the medical staff. Still, it is miserable to be sick and away from home.

It is not my goal to discourage prospective patients from seeking help in China. I merely hope that by sharing our experience and observations, it would serve as caveat emptor. Know that this stem cell treatment is not for everyone. It takes commitment and a positive outlook to make it a success. Having said that, I must point out that I have met more than one patient who is returning for a second time because of the fantastic results. The folks here, both medical and administrative, have been more than kind in catering to all of our wants and needs. As for Richard and I, we are optimistic that this trip is going to be a fruitful one but still, we are counting the days until we go home.

Room with a View ...

2007-03-26T23:30:00.000-07:00

I couldn't help but provide a little color in this post. Ernesto, you asked for them, here they are. This is the view from our window. One thing is that this is a growing urban area. Aside from the din of traffic and "horn rage" (as George Arruda called it), there is the incessant clanging of construction machinery. Expect to be awoken on most days by 7 am by these sounds. Oh well ...

One step forward, two steps back

2007-03-26T04:50:00.000-07:00

Richard is still plagued by headaches. I guess we rejoiced too soon Friday night thinking that he has dodged the bullet. We've found that the headaches strike whenever he has to sit up for any extended amount of time and all he has to do is lie down to make the pain go away. Tylenol helps too. By experimenting, we've found that the same triggers for migraines also produce Richard's headaches. These are loud noises, bright light, abrupt lateral movement of the head and being in a stuffy room. When he gets horizontal in a cool, dark and quiet room, he recovers in a fairly short time.

The morning acupuncture session was uneventful. I told big Dr. Lee about Richard's headaches. He said that it is important that Richard not attempt to sit up too quickly which may make him dizzy and lead to dangerous falls. This advice was echoed by "young" Dr. Yang (as opposed to the "old" Dr. Yang who is the supervising doctor who saw Richard last Tuesday) earlier this morning. Dr. Yang explained that the pressure in the spinal fluid has been disturbed by the lumbar puncture and that in turn caused the headaches. He said that it was imperative that Richard get enough rest before the next lumbar punch.

The afternoon PT session went well but the OT session was interrupted when Richard became nauseous and sweaty and had to go back to our room. The doctor on call prescribed a painkiller while the nurse came to take Richard's temperature and BP which was slightly elevated. After resting in bed, his BP went back to normal and his nausea subsided. We're mindful of Kim Poor's advice to stay hydrated but drinking more water means Richard needs to make more trips to the bathroom which can become a problem at night when he's groggy with sleep. At home, he's spoiled because our ADA bathroom can accommodate a wheelchair without a problem. Over here he needs to park his wheelchair outside the bathroom and then lean his head against the wall (we call it the Yukiko maneuver --- thanks to our friend Yukiko who showed Richard how to do it) to steady himself to sit on the toilet.

It's now close to midnight and it has just stopped raining. The air is refreshingly cool and crisp. I left the window open and there's a nice breeze wafting in. Outside the hallway, it is still a little stuffy. I went to the common room a short while ago to fill my water bottle and was surprised to find quite a few people there. I spoke to Sue who is from England. She's waiting to call her two daughters on Skype. Because of the time difference, she has to stay up until this hour to be sure to catch them at home. I found myself missing family, friends and home late at night when all's quiet. I see that I'm not alone. Tomorrow, Richard plans on posting some photos that he has taken of Nanshan.

The American Patient

2007-03-25T01:29:00.001-07:00

By posting in the late afternoon Shenzhen time, the datelines on our posts are finally in sync with the events of the day. Richard has decided to leave our Mac on California time so it is forever 15 hours behind Shenzhen.

It has been a difficult day for Richard. He looked pale when he got up this morning and started to sweat profusely. He was wearing a short sleeve t-shirt and light sweatpants. I had put the air-conditioner on overnight so the room was cool. He continued to sweat throughout breakfast while developing a runny nose at the same time. Then he got a bad headache and had to lie down. I gave him some Tylenol. His face had taken on a waxy sallow look and his skin felt clammy to the touch. I went to get the nurse. She verified that Richard did not have a temperature. She asked if Richard had stayed flat on his back for 6 hours after his injection on Friday and I told her that he did. We let him drift off to sleep and he slept for the next few hours and woke up for lunch at one o'clock.

He looked visibly better and had stopped sweating. His color had returned. His face was pinkish in color and the dark circles under his eyes were barely visible and his headache was almost all gone. After lunch, Richard decided to take a short walk around the floor. He has not used his walker since we got here. It took him quite some effort to ambulate the length of the hallway. I should mention that he had fallen in the shower the previous night and scraped his right knee on the hard rubber mat on the floor. He had slipped off the small round stool that he sat on in the shower. Because of the neuropathy in his hands and feet, it did not hurt him much but the knee was visibly bleeding.

I am speculating that because we had so many visitors yesterday, Richard did not have a sufficient amount of rest and this resulted in the set back today. I will make sure when he gets his next lumbar puncture on Wednesday that he gets enough rest the day after the procedure. Right now, he is in bed watching the movie, The English Patient. We get many Chinese channels (both Cantonese and Mandarin) on the TV in our room. There is even a Chinese MTV channel and a channel that's in English. We watched "The Closer" yesterday. So far, we've not seen any American programs that have been dubbed in Chinese. You haven't lived yet until you've seen Bugs Bunny dubbed in Italian as we had in Switzerland!

Similarities and Differences between Nanshan Hospital and Hospitals in the US

2007-03-24T03:53:00.000-07:00

Earlier on Saturday, we had some family members visit us here in Nanshan. I think we're one of the few patients in the Stem Cell Ward who have relatives living nearby.

It struck me that bringing meals to the patient is expected in many hospitals around the world. The smells and aromas of the food permeate the entire floor. In a recent phone conversation with my sister, she asked, "Where is Lily staying?" I responded, "In the same room." In the US, that just isn't done. It is not unusual in China and Hong Kong that the hospital would allow a caregiver to stay overnight in the room with the patient. Another difference is the fact that Nanshan does not have a centralized meal service for the patients. At least, I have not seen meals being delivered from within the hospital to the inpatient wards. The patient is left to find the means to feed himself. There are a lot of take-out places that would deliver to the room and the restaurant downstairs will also make deliveries.

Now for some of the similarities. The "technology" available is plenty adequate. At Nanshan, there is a blend of new and old ---- MRI's and acupuncture can be found at the same facility. Is a motorized patient bed that reclines that different from a hand cranked one or does iodine as a disinfectant (which stains) versus disposable alcohol wipes matter that much?

What is unique about Nanshan's Stem Cell Ward? There are about 20 rooms on the floor. Each room can accommodate three beds, but one patient gets to use the entire room. The rooms are very bright and spacious. We are very fortunate to have Wi-Fi reception in our room because our room is adjacent to the common room where the internet connection is. Most patients bring their laptops into or use the computers in the common room in order to surf the net. Also, Nanshan is one of Beike's first and well established locations. Especially for English speaking patients, Shenzhen's close proximity to Hong Kong means a good availability of English speakers.

Sorry to keep you waiting but Kwan Yin was calling

2007-03-23T09:49:00.000-07:00

Every day when Richard and I ride the elevator, a disembodied female voice pleads "sorry to keep you waiting" every time someone presses the "door close" button. It is no exaggeration to say that each of the eight elevators at Nanshan is packed to the gills most hours of the day. (and night) During rush hour, the elevator stops on every single floor in this 21 floor building. Jockeying for space is not for the timid. But what struck me is the serendipity that I'm hearing an English speaking voice in a Japanese-made (Mitsubishi) elevator in China.

Richard received his first lumbar puncture yesterday afternoon. The stem cells arrived around four o'clock. Richard was one of the six or seven patients scheduled for the procedure. Everything went very smoothly, he was in and out in less than half an hour. Afterwards, he had an IV in his hand from which he received growth factors to help the newly injected stem cells "take" to his body. He spent the next six hours flat on his back. At 10:30 that evening he wolfed down the takeouts that I've warmed up for him.

Today he woke up refreshed but somewhat groggy from having slept so much. I noticed that there is a rosy glow to his face and his eyes looked exceptional bright. He said he felt rested but other than that, he did not feel anything different. Big Dr. Lee and Dr. Ye both have the day off, so we did not have acupuncture, PT and OT today. Richard rested on and off while visitors like my mother, sister-in-law, cousin and Mary Ann O'Donnell dropped by. Mary Ann discovered our blog and mentioned it in one of her posts which in turn led to the Salon.com article. She came by to talk to us and other patients on the floor and was also given a tour of the facilities by the Beike staff.

Richard had a tough time resting during the day because of the noise from the construction site across the street. We were told that a new Shenzhen Metro stop is being built there. The hospital is very close to the city government center. The Chinese restaurant at the Xin Tao Yuan Hotel across the street is apparently the preferred place for power lunches of the city's bureaucrats. From the window in our room, we can see lots of new buildings and a highway overpass in the distance. Shenzhen is growing at an enormous pace. Its labor is supplied by young people from all across China. I read somewhere that the average age of a Shenzhen resident is 25. This melting pot of migrant workers results in restaurants serving virtually every regional cuisine imaginable.

A few nights ago we went for a stroll with my mother who is visiting us from Hong Kong. We saw two men dressed in Buddhist saffron robes squatting by the sidewalk near the hospital. They were talking in an animated fashion with some pedestrians. My mother said that the monks were telling the fortunes of the passersby for a fee. The Goddess of Mercy, Kwan Yin, is believed to whisper secrets of the future to the monks whom she favors. It is these secrets that the monks are now divulging to their paying customers. Apparently the goddess was a lousy judge of character because my mother saw these holy men last night eating BBQ meats, chugging down copious amount of beer and chain smoking in the restaurant at her hotel.

The Yellow Brick Road to Shenzhen

2007-03-22T18:11:00.000-07:00

I forgot to post this one earlier... Richard

We took a direct flight across the Pacific that arrived in the early morning on Monday (6:30 AM). By 9AM we had arrived in Nanshan.

We opted for ground transportation from Hong Kong airport instead of the ferry to Shenzhen. A mini-van came to pick us up and we never left our seats once we boarded as the driver handled the customs at the border crossing. We still needed to get the visa to China, but Hong Kong has no visa requirement for Americans.

Also long gone are the drab olive green uniforms of the Chinese border guards that is reminiscent of the PLA when Hong Kong was under British control. Now the guards wore smart, form fitting dark blue duds. In the interest of commerce and efficiency, the customs process is much more streamlined as there are many more commuters between Hong Kong and Shenzhen. The only major traffic jam that we encountered on the way was in Shenzhen.

You don't want to drive between Hong Kong and China. Aside from the dense traffic and aggressive drivers , Hong Kong still drives on the left side of the road while in China one drives on the right.

I am looking out our window now and the same hazy sky persists. It only rained Monday morning since we arrived. I can't tell which way is north since I haven't seen the sun!

Later today (Friday) is the first stem cell injection.

Fly on the wall

2007-03-22T02:26:00.000-07:00

I've had my share of hospital stays in the United States. Much of daily life in a hospital can be summed up as "hurry up and wait". It is very much the same here in Nanshan except for a cultural twist.

The department of rehabilitation at the hospital is quite large and has the reputation of being the best in the area in terms of specialized equipment and medical personnel. As a result, there are many outpatients who are treated here daily on a first come first serve basis. Factor in the twenty of so patients in the Stem Cell Ward and other patients in the hospital and you have a scheduling problem that rivals chaos theory. And yet, to my amazement, we never had to wait for more than 5 to 10 minutes for Richard's daily appointment.

Richard's PT, OT and acupuncture treatments are performed in three separate areas. The acupuncture and Chinese massage (Tui Na) area has around ten narrow cots laid out in close proximity to each other. Each cot can be curtained off from the rest of the room. Almost every patient that I've seen in the last three days is accompanied by one or more companions. You do the math. Twenty people plus up to five therapists coexist in the same room. There is absolutely no privacy. You can hear every word that's spoken. The privacy curtains are rarely used. Despite all this, there is almost a spa-like atmosphere to the place. It felt cozy rather than claustrophobic. Total strangers banter back and forth. The foreign patients used the time to catch up with each other. Though I must admit that the locals love to stare openly at the foreigners in the room. For a while, I had the dubious distinction of being the star attraction:

Richard and my entrance to the room barely caused a ripple of interest since we blend in with the locals. I then address Dr. Lee in Chinese to let him know that Richard is ready for his treatment. So far so good. As Richard settles into his cot, Dr. Lee comes over to apply the needles. I start to wander off to chat with the other patients and caregivers from our floor. The first time I did this, heads swivelled. After a while, I noticed that some people from the next room which is the PT gym area started to migrate over to stare at me through the open partition between the two rooms. Good lord, she looks Chinese, she speaks Chinese but she's really a lao why (foreigner in Chinese, but it mostly refers to Caucasians)!

The OT room is run by an all female staff. Dr. Ye and her staff share a soft spot for the children under their care. I asked Dr. Ye about the incidence of autism in China. She told me that she has seem her share at the hospital. Her heart goes out to the parents of these children. She showed me a photo of a young, autistic Australian boy who she's treated. He was a little over one year old when his parents brought him to Nanshan.

Nanshan (or Shenzhen People's Hospital Number 6 as it is officially known) is a teaching hospital. On a regular day, there are quite a few interns getting their hands-on experience in the rehab department. They work under the watchful eye of the doctors. There are two Dr. Lees in rehab. "Big Dr. Lee" is the supervisor of acupuncture, Chinese massage and PT. He got his moniker since he is larger in physique (taller) than "small Dr. Lee" who coincidentally came from the same city as Richard's parents. Big Dr. Lee is often frustrated by the antics of some of his interns. The young 'uns apparently tend to bite off more than they can chew in order to one-up each other. When one of them tried to emulate the way that Dr. Wang, another doctor in the PT department, threw the ball to Richard the previous day, Richard started to keel backward. Luckily, big Dr. Lee was watching through the open partition. He started to yell at the intern to quit showing off and to stick to the basics like making sure that the patient does not fall down.

In the spirit of what's good for the goose is good for the gander, I decided to seek Dr. Lee's help in getting rid of my chronic neck, shoulder and back pain. He prescribed heat treatment, the electric stimulation machine and Chinese massage and kindly squeezed me in as the last patient of the day. As a result, I not only got effective pain relief but also a telling glimpse of the closeness between the interns and the doctors.

I was lying on my cot in the empty acupuncture room waiting for my muscle stimulation machine to finish the program when in came three interns. It was five thirty-three in the afternoon, a little past quitting time. It has been a long day for the interns. A female intern pleaded with a male intern for massage relief on her sore neck. He replied that he can do better than that --- he was going to do his "famous" neck adjustment for her. She protested vehemently that he had not gotten the doctor's approval to perform the delicate maneuver. The young man waved off her objections and started to massage her neck a little too roughly. The girl squealed and told him to be more gentle.

Meanwhile, the other male intern wandered over to fan the flames. He said that he does the neck adjustment better than anyone else and he'd be willing to do it. Just as the girl was starting to panic, little Dr. Lee walked in and asked what was going on. He listened with an expression of mock gravity and went over to the girl. He then put his hand on her neck and carefully performed the adjustment. The interns watched in a respectful silence that was broken when another female intern rushed in to ask the doctor for permission to leave for the day. I have a feeling that all these interns are going to make fine doctors one day. Yes, I would even ask any one of them for a neck adjustment.

Babelfish in iPod City

2007-03-21T05:08:00.000-07:00

Hi, this is Richard here! Lily "guest-wrote" the last four posts so I felt that I should be doing my share. I am more of a computer geek while Lily and Andrea possess a literary flair. Case in point: instead of calling the earlier post "What time it is in Milan?", I would've chosen something you'd read out of a computer manual like "Day 2- .... ".

With that said, I cannot thank my wife enough for using her fluency in Cantonese and Mandarin to help me ease communications with the staff at the hospital. By the way, the correct way to refer to the official language in China is Putonghua (literally, the common language). At physical therapy today, Dr. Lee gently chided me when I said my one and only phrase in Mandarin,"I do not speak Mandarin" to him . He told me that since Mandarin or Guo Yu, means language of the country, it therefore includes all dialects of China. Because I spoke Cantonese, (albeit very limited) I cannot say that I do not speak Mandarin.

While most of the staff here speak some English and a large portion of the patients (at least while we're here) are from English speaking countries, "lost in translation" is a daily affair. However, any effort to communicate is welcomed by both parties. Hand gestures like a thumbs up are readily understood. If one can secure the services of someone to help translate during the first few days, that would be tremendously helpful.

IPOD City in the title of this post refers to Shenzhen where many of the IPODs are manufactured. In fact, you can have your IPOD engraved for free when you order it through APPLE. It will be shipped to you direct from Shenzhen.

What time is it in Milan?

2007-03-20T07:58:00.000-07:00

Between the hard beds and jet lag, we slept rather poorly last night and got up at six in anticipation of an agenda-packed day. The nurse came to get Richard's blood pressure, and blood, urine and stool samples. Then we were shepherded with an Italian family to the outpatient department for tests. Richard had electromyography which tests the muscles of his legs and feet.

After that, Dr. Yang (not the same Dr. Yang from yesterday) who is the supervising physician, came with the other interns to take a comprehensive medical history and performed more motor tests on Richard. Then we rushed down to start acupuncture with Dr. Lee. Electrical current was applied to the needles to stimulate the muscles. All of Richard's needles were put on his legs. The movement of the muscles of his legs made the needles quiver rhythmically. Richard said that he only felt a slight prick when the first needle went in and after that he was not aware of the other needles going in at all. The stimulation from the electrical current was quite bearable as long as Dr. Lee receives continuous feedback as to what was Richard's comfort level.

Physiotherapy came next. The same Dr. Lee prescribed and had Richard perform various isotonic exercises using 5lb. weights in each hand. Dr. Lee emphasized that he was looking for both stability and strength in these exercises. Luckily for Richard, our Pilates instructor, Karen, had coincidentally been having us do the same movements for the last couple years so it was par for the course. By the end of PT, Richard was quite exhausted.

After lunch, a quick nap, and an EKG, Richard attended the second half of his PT session. This time, he practiced throwing and catching a ball with his therapist. Then Richard was asked to walk heel to toe while holding onto parallel bars. It has been a long time since he has walked without the help of his walker but he managed commendably. After this, we went to occupational therapy with Dr. Ye. She evaluated Richard's handwriting which has deteriorated progressively over the past few years. As she massaged Richard's arms and hands, she had him perform a series of exercises using special equipment to strengthen the fingers. At the same time, she put a collar-like device around Richard's throat. The electrical current through the collar was suppose to stimulate the throat muscles and help with swallowing and speech. Later on, Richard amused the other patients in the OT area when he was asked to pick up marbles with chopsticks. This he did with the patients' and Dr. Ye's beaming approval.

Dr. Guo who is in charge of the stem cell injections came by to introduce herself and to confirm our request for four lumbar punctures and one IV. Richard's first stem cell lumbar puncture is scheduled for this Friday. We were told that he needs to rest up in order to improve the effectiveness of the treatment. In an attempt to get a good night's rest, Richard took an Ambien and is now acting out his dreams. I've never seen such a volley of rapid movements in his fingers, hands and arms. This is different from his usual myoclonus when the whole of his upper body jerks forward violently. I am wondering if taking the Ambien is such a good thing. Dr Perlman, if you happen to be reading this post, can you comment to let us know if Richard should stop taking Ambien?

The Eagle has landed

2007-03-19T02:00:00.000-07:00

Hello everyone! We’re here at the Nanshan Hospital in Shenzhen. Logistically, it was no small feat traveling with 4 suitcases, a wheelchair, walker, CPAP machine and backpack. But we made it!

Hong Kong was drizzly this morning and the temperature was pleasantly cool. The efficiency of the airport staff in Hong Kong never ceases to amaze us. We landed at 6:30am and were ready for pick up curbside by 7:00am. Shenzhen has gotten even more cosmopolitan since Richard last visited in 2002. There are high rises everywhere and the traffic rivals that of LA.

Our first day on the 14th floor (the stem cell ward) is kind of like the first day at college. You are shown your room by people who are essentially the RAs, except at Nanshan, they are the liaison and administrators. There is a tour of the common, kitchen and laundry areas. We also met some of the other “kids” on the floor. There are patients from all over the world --- Brazil, Romania, Italy, Singapore, Scotland and the United States.

Dr. Yang came by shortly after we arrived to take Richard’s medical history. Temperature was taken in the axillary fashion. Then we were given a tour of the Physical Therapy, Occupational Therapy and electro-simulation areas. Next, Richard’s eyes were dilated and the fundus photographed. By this time, jet lag hit Richard hard and when he got back to the room, he climbed in bed for his well-deserved nap.

Tomorrow’s agenda includes blood tests, some sort of leg muscle test and the start of his PT, OT and electro-stimulation. Stay tuned!

15 minutes of fame

2007-03-16T21:06:00.000-07:00

Our friend Kevin alerted us to an article in today's Salon.com that mentioned this blog and our last post. If you are interested, click on the "The Stem Cell Blogs of China" link under "Links of interest" in the right hand column. We are very excited to see that there is growing interest in stem cell therapy in China, and we are honored that we can help put a more human face to this issue.

It takes a village

2007-03-15T12:08:00.000-07:00

The Chinese proverb says that a journey of a thousand miles begins with the first step. In our case, our trip to China started with the help of many individuals who either directly or indirectly steered and guided us to our present course. Lily’s Aunt Lucy researched tirelessly on alternative Chinese medical treatments and urged us to explore these possibilities. At the same time, the MJD family provided us with valuable information and updates about the disease and ground breaking studies. We want to thank Mike Fernandes, the pater familias of the Northern California Ataxia Support Group, and Deb Omictin for letting us know that we are not alone. Also, muito obrigado to Fernando Santos for moderating and overseeing the exchanges on the MJD online discussion board. Then there is Kim Poor whose trip and blog serve as the touchstone for those who follow ---- Kim, thank you! George (and his wife, Melissa) Arruda, who followed, are equally inspirational. In fact, it was George’s sister, Celia’s, eloquent remarks on Chinese stem cell therapy on the MJD discussion board that convinced us to go on this trip.

Much closer to home in the Bay Area, we would like to thank Ken and Veronica for helping us get in touch with Dr. Roger Kornberg and to Chris for the good health talisman. We are grateful for Jane Ellen's and Ivy's help in looking after the house while we are gone. Our plants get a mini vacation thanks to I-Ching and Baker. We'll also be thinking about (and thanking) Arianna every day during our trip for the profusion of vitamins that she has selected for us. Many thanks to Kevin, Michael, Ken, Kim, Rita, Pushpa and Jackie for having lunch with us this week, and also to our friends and family both near and far who sent us their good wishes.

We were treated to a fantastic sending off party last night at Jeanne and Randy's. We'd like to thank our wonderful hosts and hostesses, Jeanne & Randy, Cathy & Peter, and all of our friends, Ann & Peter, Julia & Bob, Pushpa & Sharad, Rita & Ramon, Kathy & Tony, Arianna & Bryan, Zann & Seana, Veronica & Ken, I-Ching & Baker, Sandy, Elizabeth, Kathleen and Jackie for their thoughtfulness and for reminding us of what we'll be missing while we're in China. Here are a few photos of last night's festivities.

Last but not least, we want to thank our daughter, Andrea, for being a crucial (and at times, quirky) part of our lives and for her scholarship that took the financial sting out of this trip.

Lily is reminded of the tale of a songbird that came down with a sore throat one day. His concerned friends dropped by the bird’s nest all throughout the day, offering their sympathy and homemade remedies. That night, the bird took every pill, drank every tonic, applied every ointment and wore every talisman given to him by his friends and the next morning, he was well again. Was it all the firepower of the medications that cured the bird? We ‘d like to think that the healing magic came instead from all the love that was imbued in the medicines. Thank you everyone, we couldn’t have done it without you!

T minus three and counting until liftoff. We’ll talk to you again from the far side of the moon on March 19.

My Medications and Goals

2007-03-11T09:24:00.000-07:00

I'll touch on my current medications and what my goals are for any changes in medication as a result of this trip.

In the way of medications and supplements, thank god I do not experience any pain and have no need for painkillers. Instead, almost all of my medications are for symptomatic relief. Warning: this is not a recommendation for any particular medication. Your mileage may vary!

• Antioxidants - Idebenone, NAC, Vitamin E
• Omega-3 fish oil for energy
• Creatine for nerve health
• Fluoxetine for improvement of slurred speech symptoms
• Amantadine for improvement with ataxia symptoms
• Depakote to address night time tremors

What do I expect to change after Stem Cell Therapy in China? Actually hardly any change in medication is expected. To the extent possible, I intend to consume the same array of medications and supplements during my time in China so that any changes afterwards can logically be attributed to the stem cell treatment(s).

As stated in my second post, I will be looking for temporary improvements in upright standing/walking and reduced neuropathy around the feet. Who knows ... maybe I'll go on a follow-up visit to China in the future. Also, I've been told that the effects of the some of the medications on the aforementioned list will take a number of additional months before yielding results. In other words, none of them are expected to "kick in" while I'm in China.

My Symptoms and Exercise Regimen

2007-03-10T09:41:00.000-08:00

In this post, I thought I'd describe my medical symptoms and exercise regimen. In general, my goal for improvement focuses less on strength but more on balance and coordination. Today's entry is of interest for those who wish to learn more about about these aspects of my condition.

The most significant symptom is that my balance and upright walking have progressively worsened. I can and do use a walker on occasion. However, when at home, traveling and going outside in the evenings I mostly use a wheelchair. The second most severe symptom is fatigue. A long day is just beyond my ability, and I need a midday refresher nap to restore my energy for the latter portion of the day. Multi-tasking is out of the question now.

MJD has a significant impact on matters relating to the senses and speech. I slur my speech as I become more tired. I'll also choke on certain foods - spicy, hot, especially flaky in particular - if I'm not careful. I also experience double vision. I have prisms in my eyeglasses that help with distance viewing such as the TV. Age complicates reading small fine print in dim light, but I can still manage without glasses. I also have horizontal nystagmus (rapid, involuntary oscillation of the eyes). This is one major reason why I no longer drive.

I am now more sensitive to temperature extremes. I tolerate the cold less well than heat, which is why I prefer traveling in summer over winter. I also have poorer fine motor skills. My handwriting was not that great to begin with, but it is clearly worse now. I often write in caps to improve legibility. I do have more uncoordinated physical movements now; I'll avoid filling a glass of liquid too full, and I can't throw a ball anymore.

I suffer from neuropathy of the feet, which I interpret as a loss of sensation. I know my feet are there, and I can feel obvious sensations and movements, but I'm losing touch of the finer senses. I also experience infrequent cramping of the hands and feet. This most frequently occurs when gripping with the toes or fingers. I hope to avoid starving in China when using chopsticks!

When sleeping, I exhibit myoclonus - jerking, involuntary movements of the arms and legs. I also occasionally have night terrors - acting out dreams. Rest assured, though, that I experience no pain (unless I fall!) and do not use any regular painkillers.

To help minimize the effect of these symptoms, I make an effort to exercise during the week. Typically I go twice a week to the local YMCA for a session on the exercise bike and for strength related exercises. I also do Pilates, a form of exercise that emphasizes core upper body (trunk) stability, with my wife once a week. On other days I'll spend time on our home exercise bike. I try to stick to "balance neutral" exercises. The exercise bike I use at home and at the YMCA is a "recumbent" one where the rider adopts more of a leaning position rather than sitting upright. In the past I had tried aqua therapy, but I eventually stopped because:

• It was too hard to get to the facility (though I may try again at another nearby facility)
• The logistics of getting between the pool and the locker area seemed to be more and more hazardous as my mobility degraded
• I was losing weight, which I attributed to too much energy expended on maintaining bodily warmth despite the fact that the pool was indoors and heated

The goals of this exercise regimen is to avoid muscle atrophy and injury by disuse.

Some thoughts on the medical treatment for ataxia in the U.S.

2007-03-08T13:38:00.000-08:00

I have been seeing a local neurologist for years. He diagnosed my ataxia and completed the disability paperwork. He is very competent and compassionate but I am the only ataxia patient in his practice. That's one of the down sides of ataxia; it is so relatively rare that even specialists have hardly ever come across it. When it came to symptomatic treatment, I mostly drew blanks. Conversely, I have started to see Dr. Susan Perlman of UCLA late last year. In contrast, she is not a stranger to ataxia. Aside from being an acknowledged expert in the field, she has literally seen hundreds of patients with ataxia in her practice. She recommended a slew of medications and supplements that addressed my various symptoms ranging from swallowing and choking, slurred speech, fatigue and balance. I have experienced noticeable improvements in all of these areas since.

We just returned from a visit last week to see Dr. Perlman - for a "before" China visit. Within a month of returning, the plan is an "after" China visit. Dr. Perlman has been very interested in the goings on in China. She also described what might be reasonable goals for me after the stem cell treatment. Specifically, I would want to look for an improvement in upright standing/walking as well as an improvement in the neuropathy afflicting my feet ( a loss of peripheral sensation). I also suffer from horizontal nystagmus and double vision. However, I do not expect it to improve enough to drive again (which I stopped 1.5 years ago).

For ataxia, it is unlikely that stem cell treatment alone will be a permanent cure since the root cause of the disease isn't really addressed. The solution is the ability to alter the genetics of the afflicted. I like to think that is the work of Nobel prizes (one of which was recently awarded to Dr. Roger Kornberg for his work on genetic transcription) and a lot of subsequent clinical follow-up. The downside ... there is little attention for such a rare disease like ataxia. The upside ... ataxia shares many of the same traits and treatments as Huntington's and Parkinson's Diseases which do get more attention.

A brief introduction

2007-03-07T00:24:00.000-08:00

For those who don't know me, my name is Richard Chin. I'm born and raised in the USA. Both my parents were immigrants from Canton, China (just a few hours north of Hong Kong and Shenzhen). I'm age 48 and for the past 10 to 15 years, I've shown signs of the ataxia I inherited from my dad who passed away about 19 years ago. Due to this disease, Spino Cerebellar Ataxia 3 (SCA3), I stopped working about 4 years ago . I was an engineer by trade. I am married with one daughter. My wife, Lily, is born and raised in Hong Kong. Our daughter, Andrea, is a college student in Los Angeles. We live in the San Francisco bay area near "Silicon Valley".

What is SCA3? Also known as Machado Joseph's Disease, it is one of the inherited forms (i.e. genetic) of a movement disorder. The word ataxia means without order. Ataxic symptoms may include slurred speech, uncoordinated physical movements, imbalance, nystagmus (rapid involuntary eye movement), etc. There are over a dozen subclasses of spinocerebellar ataxia (SCA). Medically, it is a neurological disease affecting the cerebellar part of the brain. How prevalent is the disease? Within the USA, SCA is listed in the National Organization of Rare Diseases (NORD). At present, there is no cure to the disease. However, there are not only palliative drugs but also research being conducted to finding the cure.

I am slated for stem cell "therapy" at Nanshan Hospital in Shenzhen, China. My wife and I will travel to Shenzhen for our 30 day stay beginning Monday, March 19. Following the footsteps of several MJD'ers who underwent treatment at Nanshan, I am planning on five stem cell injections, 4 via lumbar puncture and one by IV.

I've wondered about the nature of this blog since it is likely to be read by a wide spectrum of people from close family and friends to total strangers who happen to see it on the Beike Stem Cells website. I've decided to make it a log of the day-to-day events leading up to our trip and our experiences while in China, rather than an intimate diary or a technical research paper.