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.
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.
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," says Dr. Stephen Waxman, the lead investigator, who is 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," he adds.
Co-authors included Dr. Matthew Craner and Joel Black of Yale and the VA. The three researchers are part of Yale-London Collaboration on Nervous System Injury and Repair.
-- By Lakshmi Bangalore
T H I S
W E E K ' SS T O R I E S
University celebrates its 303rd graduationLevin calls for U.S. to change student visa policies
International arts festival returns to New Haven
ENDOWED PROFESSORSHIPSAnthony Kronman is appointed Sterling Professor of Law
Paul Gilroy is designated as the Charlotte Marion Saden Professor
Joan Panetti named the Sylvia and Leonard Marx Jr. Adjunct Professor
New campus programs will cut costs and boost efficiency
Installation at city's historical society features tales about urban renewal
Show recalls Victorians' attempts to capture nature's wonders
Exhibit spotlights works by one of Britain's most neglected artists
Medical and nursing schools to host alumni reunions
Yale and state officials consider ways to promote smoking cessation
Poll shows state of the environment a concern for voters
Scientists identify molecule that causes irreversible nerve damage in MS
F&ES symposium will examine effects of forest certification
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