Interesting article on irreversible damage in MS

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Public release date: 27-May-2004

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Yale University

Researchers identify basis for irreversible damage in multiple sclerosis

New Haven, Conn. -- Yale researchers and collaborators have

identified molecules that underlie nerve fiber degeneration in

patients with secondary progressive multiple sclerosis (MS), a

disease that cripples nearly three million people worldwide. The new

findings are the first observations in humans of molecules that

contribute to degeneration of nerve fibers.

Researchers at Yale, the Veterans Administration (VA) and University

College London examined postmortem spinal cord tissue from patients

with a progressive form of MS in a project supported by the

Department of Veterans Affairs, National MS Society, Paralyzed

Veterans of America, and the United Spinal Association. Using

biomarkers of the damaged nerve fibers, they looked for molecular

abnormalities and found a strong link between nerve damage and the

presence of two molecules, Nav. 1.6 and NCX, a sodium channel and a

sodium-calcium exchanger.

Located on the surface of most nerve fibers, Nav.1.6 controls the

flow of sodium into the cell, which in turn triggers the activation

of NCX, a molecule that, if unchecked, imports abnormal levels of

calcium into the nerve fiber that ultimately lead to its death.

" These results are extremely exciting because they provide, for the

first time, important clues about the molecular basis for permanent

and irreversible damage in MS, " said Waxman, M.D., the lead

investigator, chair of neurology and director of the VA

Rehabilitation Research and Development Center in West Haven. " We

hope to use these results to design new therapies that will protect

vulnerable nerve fibers. "

MS is an inflammatory disease of the central nervous system in which

myelin, the insulation that surrounds the nerve fibers, is damaged in

multiple regions, leaving scars that hinder the relay of nerve

signals from the brain to the rest of the body.

One of the hallmark features of MS is a relapsing-remitting course in

some patients. There is molecular rebuilding of nerve fibers, relay

of nerve signals even in the absence of myelin, and recovery of

previously lost functions such as the ability to see or walk, as the

disease remits. Patients with the relapsing-remitting form of MS are

neurologically normal between relapses, and do not develop permanent

disability.

However, in progressive forms of the disease, entire lengths of the

nerve fibers begin to degenerate, resulting in permanent and

irreparable damage, a steady worsening of symptoms and accumulation

of disability.

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Co-authors included Craner, M.D., and Black of Yale and

the VA. The three researchers are part of Yale-London Collaboration

on Nervous System Injury and Repair.

Citation: PNAS, May 17, 2004, 10.1073/pnas.0402765101 (Early Edition)

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