Friday, November 23, 2007

MS severity linked to genetic makeup

Old drug offers new MS hope
Telegraph.co.uk - United Kingdom
Tens of thousands of people who suffer the degenerative disease
multiple sclerosis receive new hope of more effective treatments
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ms severity linked to genetic makeup
University at Buffalo Reporter - Buffalo,NY,USA
... 222 had secondary-progressive ms, characterized by occasional attacks and sustained progression; 30 had primary-progressive ms with steady worsening ...
See all stories on this topic

MS severity linked to genetic makeup

By LOIS BAKER
Contributing Editor

Magnetic resonance images (MRIs) of a large group of patients with multiple sclerosis have provided the first evidence that those with a history of MS in their families show more severe brain damage than patients who have no close relatives with the disease.

photo

This graphic shows brain MRIs of patients without MS (top row), patients with sporadic, or non-familial, MS (middle row) and patients with familial MS (bottom row).
PHOTO:

The results, based on brain MRIs of 759 consecutive MS patients, support the hypothesis that a patient's genetic makeup plays a role not only in development, but also in severity of the disease.

A UB team of neurologists and imaging experts headed by Robert Zivadinov, professor of neurology, conducted the research at the Buffalo Neuroimaging Analysis Center (BNAC), which Zivadinov directs. The BNAC is an arm of the Jacobs Neurological Institute (JNI), UB's Department of Neurology in the School of Medicine and Biomedical Sciences. Patients were recruited at the Baird MS Center, also part of the Jacobs Neurological Institute.

The research findings were presented recently at the 23rd Congress of the European Committee for the Treatment and Research in Multiple Sclerosis in Prague, Czech Republic.

"From the early 1980s on," said Zivadinov, "MS researchers thought that genetic factors likely played a role in the disease, that its traits were determined by several different genes, and our findings support this hypothesis.

"Our MRI analysis showed a difference between the severity of disease characteristics in familial MS patients versus what we call sporadic, or non-familial, MS patients," he said. "These differences may be related to some disease-modifying genes, but to prove this, we must do further investigation."

MS destroys myelin, the fatty sheath that protects nerve fibers carrying message traffic from various muscles to and from the central nervous system. For reasons currently unknown, in some people the myelin sheath breaks down, resulting in destruction of the nerve fibers and the symptoms of MS.

This demyelination process leads to mild to serious disability, from slight numbness of the limbs to loss of vision and paralysis.

The cohort of 759 patients involved in the study ranged in age from 36-56, with an average disability score of 3.4 on a scale of 0-10. A higher number indicates more disability.

Of these patients, 478 had relapsing-remitting MS, involving acute attacks with full or partial recovery; 222 had secondary-progressive MS, characterized by occasional attacks and sustained progression; 30 had primary-progressive MS with steady worsening from onset; and 29 had experienced their first attack.

Twenty-six percent, or 198, had a positive family history of MS. The breakdown between first-, second- or third-degree relatives with MS was 81/35/82. All patients obtained full clinical and quantitative MRI evaluations.

Using MRI, researchers measured the number and volume of lesions (plaques), which represent areas of demyelination; atrophy of the whole brain, white matter (the neural pathways), gray matter (brain regions) and the cortex; as well as employing additional imaging techniques.

There were no significant differences between familial and sporadic cases based on age, disease duration, disease course, disability score and total lifetime use of disease-modifying drugs.

Analysis showed that compared to patients with no family history of MS, familial MS patients had significantly more destructed lesions and significantly lower volume of whole brain, white matter and gray matter, as well as other indications of greater brain degradation.

"Patients whose parents, children or siblings [first-degree relatives] had MS showed more damage than patients who had cousins with MS," Zivadinov said. "This indicates that the closer the relationship, the greater the risk of MS.

"Of particular interest is the finding of more severe gray matter damage and more lesions, particularly in those with MS in first-degree relatives. These findings are very interesting and we will be investigating them further."

Additional researchers on the study from the BNAC and the JNI were Frederick E. Munschauer, Nadir Abdelrahman, Sara Hussein, Jackie Durfee, Barbara E. Teter, David Hojnacki, Michael G. Dwyer, Jennifer L. Cox, Marlieke De Brujin, Milena Stosic, Fernando Nussenbaum and Bianca Weinstock-Guttman.

Murali Ramanathan from the School of Pharmacy and Pharmaceutical Sciences also contributed to the research.

http://www.buffalo.edu/reporter/vol39/vol39n9/articles/ZivadinovFamilialMS.html

Cell research on fast track
Therapeutics Daily (subscription) (press release) - Newtown,PA,USA
... Alzheimer's and multiple sclerosis. A new technique that reprograms human skin cells to behave like embryonic stem cells, which can then be turned into ...
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Cell research on fast track

Herald Sun (Australia) - Nov. 22, 2007
A MAJOR breakthrough in stem cell research this week will give scientists a huge boost in the fight against complex diseases such as Parkinson's, Alzheimer's and multiple sclerosis.
A new technique that reprograms human skin cells to behave like embryonic stem cells, which can then be turned into any type of human tissue, could fast-track research on disease analysis by at least two years.
Unlike previous stem-cell research, which required the controversial use or destruction of human embryos, this new technique revealed by separate teams of Japanese and US scientists uses a genetically modified virus to convert adult skin cells into embryonic-like stem cells.
By converting these stem cells into neurons (nerve cells), scientists can observe how degenerative diseases develop in neurons in a dish. Australian Stem Cell Centre senior scientist Andrew Laslett said the breakthrough was ``fantastic''.
It provided scientists with amazing opportunities to study the progression of various diseases and test the effects of different drugs.
``If you took some skin cells from a patient with Parkinson's and some from say, his brother without Parkinson's, turned both first into embryonic stem cells and then into neurons, and then laid them side by side and watched them develop, you could potentially compare how and why one cell line developed Parkinson's and the other didn't,'' Dr Laslett said.
``This could give us some clues as to what's going wrong.''
http://www.therapeuticsdaily.com/news/article.cfm?contentValue=1612503&contentType=sentryarticle&channelID=29


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