Grant: Operating Grant - Priority Announcement: Neuromuscular Research

The signature feature of muscular dystrophy as a disease is the absence of a key muscle fiber membrane protein called dystrophin. One of the most promising therapeutic strategies for countering muscular dystrophy is to replace in the diseased muscle the missing dytrophin protein with its "twin sister" protein, utrophin, which is found in small amounts in the muscles of people that have muscular dystrophy. We have provided exciting new evidence showing that utrophin is under the control of another muscle protein, calcineurin, an enzyme that we have shown to be an orchestrator of muscle growth. Indeed, we showed that when calcineurin is turned on within a muscle fiber, utrophin is enticed to appear in abundance all over the muscle fiber in areas usually reserved for dystrophin. By virtue of this replacement calcineurin is thus capable of rescuing fibers that are damaged by muscular dystrophy. Within the time frame of this proposal, we plan to further define the role of calcineurin in this rescuing of damaged dystrophic muscles and plan to identify other players in this symphony to help us to better understand and develop strategies and interventions to reverse its damaging effects.