MDA awarded a research grant totaling $328,153 over a period of three years to Kenneth Hensley, associate professor in the departments of pathology and neuroscience, and research director in the department of pathology at the University of Toledo Medical Center in Ohio. The funds will help support Hensley’s study of a potential new target and treatment strategy for amyotrophic lateral sclerosis (ALS).

Recent findings from Hensley’s laboratory and from other groups, Hensley said, suggest that ALS actually begins near the junction of nerve and muscle (the neuromuscular junction, or NMJ).

“We hypothesize that molecules called semaphorins acting inappropriately near the NMJ signal axons, the long fibers that extend and carry information away from the bodies of motor neurons (nerve cells). The semaphorins’ signals cause the axons to move away from the muscle and ‘collapse’ backward toward the spinal cord.”

Research conducted by Hensley and colleagues implicates a protein called collapsing response mediator protein-2, or CRMP2, in this process of axon degeneration. The group will now test three distinct pharmacological (drug-based) approaches to interrupting CRMP2-dependent axon degeneration in the SOD1 research mouse model of ALS.

“We have invented and patented small molecule compounds called lanthionines that bind CRMP2 and inhibit or reverse CRMP2-dependent axonal degeneration,” Hensley said.

The investigators also are researching antibodies that could be administered to people with ALS, where they would block semaphorin binding to neural receptors and prevent the inappropriate activation of CRMP2 pathways.