Postdoctoral research scholar Bogdan Beirowski, in the department of genetics at the Washington University School of Medicine in St. Louis, was awarded an MDA development grant totaling $180,000 over three years to study how defective Schwann cells lead to nerve-cell damage in Charcot-Marie-Tooth disease (CMT).
MDA development grants are awarded to exceptional postdoctoral candidates who have the best chance of becoming independent researchers and future leaders of neuromuscular disease research.
Degeneration of axons — fibers that carry electrical signals between the brain and spinal cord and the rest of the body — is a hallmark of CMT and some forms of Dejerine-Sottas disease, and is thought to be responsible for muscle weakness associated with these diseases.
In some forms of CMT, the primary molecular defect localizes to Schwann cells, which normally help nourish and protect axons by wrapping them in a multilayered membrane called myelin. But it's poorly understood how Schwann cell dysfunction causes axon damage.
Data from previous work suggests that removal of defective myelin (demyelination) causes inflammation that results in axon damage, but Beirowski hypothesizes that "defective Schwann cells deprive long axons of metabolic support, thus contributing to axon degeneration."
Beirowski has developed mouse models in which key metabolic regulators are blocked exclusively in Schwann cells, which he now will use to test whether failure of the cells to deliver nutrients to axons could explain axon loss.
The identification of specific metabolic defects in Schwann cells could lead to the development of CMT therapeutic strategies based on supporting the stability of axons.
Funding for this MDA grant began Aug. 1, 2012.