MDA has awarded a research grant totaling $420,000 over three years to Thien Nguyen, assistant professor in the department of neurology at Johns Hopkins University School of Medicine in Baltimore. The new funds will help support Nguyen’s research into the breakdown of peripheral nerves (nervous tissue that connects the spinal cord with muscles and sensory organs) in Charcot-Marie-Tooth disease (CMT).

Degeneration of the axons (the long fibers that carry signals from nerve cell bodies to muscle) is a hallmark of type 1 CMT and is the primary determinant of the severity of symptoms in people with the disease. It follows that prevention of axonal degeneration should improve clinical outcomes for people with CMT1.

The same principle also should be applied to other types of CMT, Nguyen noted.

In previous studies, Nguyen and colleagues have determined that mutations in genes for myelin-making cells called "Schwann cells" can lead to mutant Schwann cells that may instruct axons to degenerate through certain specific signaling molecules that normally promote stability and survival, including one called myelin-associated glycoprotein (MAG). Study results out of Nguyen's lab have suggested that another signaling molecule, called netrin-1, may play an important role in axonal survival in CMT, making it a potential therapeutic target.

The investigators will determine whether increasing netrin-1 activity might prevent axonal degeneration in cell culture and in a research mouse model.

Findings from Nguyen’s work could reveal the potential therapeutic benefit of netrin-1 and lead to its development as a neuroprotective therapeutic for CMT.

"In theory, results from the project also could be expanded to axonal degeneration even without demyelination," Nguyen said. "Thus, there could be applicability to many of the neurodegenerative disorders covered by MDA."

Funding for this MDA grant began February 1, 2011.