Machado-Joseph disease

[lynnifer]

An interesting article of a condition I've personally never heard of, nor is there a cure for it. He is raising funds to go to China for stem cell treatment at (Bieke Biotech) Hangzhou for cells from umbilical cords. The article states they will be injected directly into his CSF at a cost of $23,000. Acupuncture and intensive physiotherapy are also part of the regimen. They will be holding fundraisers in the coming months. He is married with two boys; 8 & 10 as well as a daughter who is 19.

http://www.canada.com/windsorstar/ne...981a51&k=21070

Hope for man's rare illness lies across the globe

Friends rally to raise cash


Gloria Bacci, The Windsor Star

Published: Monday, July 09, 2007


Trevor Dyett loves spending time with his two sons on the basketball court and the baseball diamond.

But over the past year, it's become increasingly difficult for Trevor to keep up with his boys, Tyler, 8, and Treyvohn, 10.

"I was seeing drastic differences in myself," said Trevor, who also has a 19-year-old daughter, Tempest.

Trevor started to experience leg cramps, lack of balance and weakness in his limbs.

After undergoing genetic tests last September, he was diagnosed with Machado-Joseph disease, a rare hereditary illness involving progressive deterioration of the central nervous system, for which there is no known cure.

The degenerative disease is characterized by walking and balance problems, slurred speech and numbness, said Dr. Mary Jenkins, a movement disorders specialist at the London Health Sciences Centre.

[Wise Young]

Hi, Lynnifer, Machado-Joseph Disease is just another name for spinocerebellar ataxia. It is an autosomal dominant degenerative disease, involving the cerebellum. In other words, the person gets the disease if he/she receives the gene from one of the parents. Unlike most other disease names, Macado-Joseph are not named after the doctors who first described the disease but rather after two Portuguese/Azorean families that have the disease and immigrated to Massachusetts in the 1970's. Its acryonym is MJD.

MJD results from a mutated gene is called ataxin-3 on chromosome 14q. The mutation is a repeated triplet. Affected cells accumulate the ataxin-3 protein that eventually kill the cells. The earlier the appearance the disease, the faster the progression and severity of the symptoms.

The disease is categorized into three types. Type I begins at ages 10-30 years, Type II at 20-50 years, and Type III at 4-70 years. The symptoms are dystonia, spasticity (continuous and uncontrollable muscle contractions), spastic gait, and hyper-reflexia. There may be pain and unpleasant sensations. Most have double (diplopia) or blurred vision, loss of color vision, and inability to regulate eye movements. Some have Parkinson-like symptoms. There may be sleep disturbance, cramps, and urinary bladder dysfunction.

Treatment is largely symptomatic. It is difficult to image why cord blood cells would be beneficial in this disease. There is some evidence that umbilical cord blood cells may be beneficial in genetic diseases where a particular enzyme may be missing and the cord blood cells may provide this enzyme. For example, Joanne Kurtzberg at Duke University reported last year that children with a fatal genetic disease called Krabbe Disease can be saved with early infusion of HLA-matched umbilical cord blood. (Source).

In Krabbe disease, the children are missing a critical enzyme that is necessary for forming myelin sheaths. The cord blood provides that enzyme to allow myelination in the children. While it did not reverse the symptoms of this deadly disease, the cells prevented progression of the disease in the children and saved their lives. As Kurtzberg pointed out, time is of the essence because the treatment must be given as early as possible.

Over 45 genetic diseases have a deficit of enzyme and potentially may be able to benefit from umbilical cord blood cell transplants. These include diseases such as Krabbe disease, Hurler Syndrome, Adrenoleukodystrophy (this is the disease in the book/movie Lorenzo's oil), metachromatic leukodystrophy, Tay-Sachs disease, Sanhoff disease, and others.

It would be very interesting if cord blood cells turn out to be beneficial in an autosomal dominant storage disease such as MJD. The mutated protein accumulates in the cells and cause their early death. Some triplet repeat diseases (Source) in non-coding regions include Fragile X syndrome (one of the most common causes of mental retardation), Friederich ataxia, myotonic dystrophy, and spinacerebellar ataxia type 8 and 12. Diseases with triplet (Cag) repeats in coding regions include spinobulbar muscular atrophy (Kennedy's disease), Huntington's disease, Dentatorubral-pallidoluysian atrophy, and spinocerebellar ataxia types 1, 2, 3, 6, and 7.

For more information, see http://www.ninds.nih.gov/disorders/m...ado_joseph.htm

Wise.

[MioaraD]

Dr Wise
I have seen in Shenzhen 3 people with ataxia that had spectaculous results with s/c treatment to the extent that 1 did not use the w/c anymore after 1 st treatment & after the 2nd treatment even the walking frame & cane were not needed anymore.

[Wise Young]

Dr Wise
I have seen in Shenzhen 3 people with ataxia that had spectaculous results with s/c treatment to the extent that 1 did not use the w/c anymore after 1 st treatment & after the 2nd treatment even the walking frame & cane were not needed anymore.

Thanks, it will be very interesting to see the results. Wise.

[Sue Pendleton]

Treatment is largely symptomatic. It is difficult to image why cord blood cells would be beneficial in this disease. There is some evidence that umbilical cord blood cells may be beneficial in genetic diseases where a particular enzyme may be missing and the cord blood cells may provide this enzyme. For example, Joanne Kurtzberg at Duke University reported last year that children with a fatal genetic disease called Krabbe Disease can be saved with early infusion of HLA-matched umbilical cord blood. (Source).
In Krabbe disease, the children are missing a critical enzyme that is necessary for forming myelin sheaths. The cord blood provides that enzyme to allow myelination in the children. While it did not reverse the symptoms of this deadly disease, the cells prevented progression of the disease in the children and saved their lives. As Kurtzberg pointed out, time is of the essence because the treatment must be given as early as possible.

Over 45 genetic diseases have a deficit of enzyme and potentially may be able to benefit from umbilical cord blood cell transplants. These include diseases such as Krabbe disease, Hurler Syndrome, Adrenoleukodystrophy (this is the disease in the book/movie Lorenzo's oil), metachromatic leukodystrophy, Tay-Sachs disease, Sanhoff disease, and others.

Wise, a large sub-group of those who have acute Transverse Myelitis are 6 month old infants to 3 year old toddlers. Any chance if cord cells can help genetic diseases that they might help children who are still producing myelin recover more than without treatment other than MP and/or plasmaphresis (cleaning the blood)? As I understand it most children continue to produce myelin until about age 3.
Sue

[Wise Young]

Wise, a large sub-group of those who have acute Transverse Myelitis are 6 month old infants to 3 year old toddlers. Any chance if cord cells can help genetic diseases that they might help children who are still producing myelin recover more than without treatment other than MP and/or plasmaphresis (cleaning the blood)? As I understand it most children continue to produce myelin until about age 3.
Sue

Sue,

Yes, TM is most common in young kids. Over 100 cases per year in Australia per year, I believe. I wish that I knew what the cause is. It may be inflammatory, ischemic, or immune.

One of the most interesting potential effects of cord blood cells is that they appear to be anti-immune, as are mesenchymal stem cells. For a long time (and even now), doctors did not know why one does not have to match HLA antigens exactly to get engraftment of umbilical cord blood cells. For example, even 4:6 HLA matched cells will result in 80% engraftment while one needs perfect 6:6 HLA matched cells to get similar engraftment rates for bone marrow stem cells.

It is not becoming apparent that umbilical cord blood cells may have anti-immune effects, i.e. they turn off the immune response. It also appears that mesenchymal stem cells from bone marrow will do the same. Because they turn off the body's immune system, they prevent rejection, at least for a time. This allows the cells to survive and even proliferate for a while. The theory now is that the cells then release growth factors that stimulate regeneration and repair.

So, yes, there may be some rationale of such cell transplants in TM, I believe. The cells may be able to stop auto-immune attacks or inflammatory attacks. Second, they may stimulate faster repair and even regeneration. I think that they should do clinical trials to test this.

Wise.

[Sue Pendleton]

I'll pass the clinical trial idea on to some friends. With small children it is almost always cervical level and putting 1 year olds on vents is heartbreaking.