The CMT Research Foundation is collaborating with patient-based drug discovery platform company AcuraStem and renowned expert in CMT Dr. Alessandra Bolino to test a novel PIKfyve inhibitor for its ability to prevent disease in CMT4B1. This particularly severe form of CMT usually begins before a person’s third birthday, frequently leads to wheelchair use, and can even cause death from weakening of the muscles that control breathing.

CMT4B1 is caused by mutations of the gene MTMR2, which leads to excessive levels of a fatty substance called PI(3,5)P₂. This in turn causes the myelin sheath to become misshapen and dysfunctional, quickly leading to nerve degeneration. Because this fatty substance is normally produced by the enzyme PIKfyve, inhibiting the activity of PIKfyve may lower PI(3,5)P₂ levels to normal, thereby warding off nerve dysfunction and preventing the symptoms of disease. This two-year project will test the new PIKfyve inhibitor in both cell models and rodent models of CMT4B1.

This project has successfully passed its first stage, a series of tests to ensure that the drug candidate travels to the peripheral nerves in healthy animals and inhibits PIKfyve in the cells there. Furthermore, stage one resulted in finding a series of dose levels that are expected to be safe and effective in stage two of the research, a preclinical trial of the drug candidate in CMT4B1 mice.