Eric Hoffman, director of the Research Center for Genetic Medicine at Children's National Medical Center in Washington, D.C., was awarded an MDA research grant totaling $321,659 over a period of three years to study whether a process called asynchronous repair contributes to muscle degeneration in Duchenne muscular dystrophy (DMD).
Normal muscle repairs itself following injury, Hoffman points out, and that repair is a coordinated process within the muscle, taking place over about two weeks. “Our model is that muscle repair in DMD is asynchronous: Different regions of DMD muscle start the repair process at different times, and neighboring regions of the muscle get disoriented as to which time point in the two-week time frame of repair they are in. This results in inappropriate signals and failed regeneration.”
The implication of that model is that resynchronizing the repair process should provide therapeutic benefit. Hoffman has data suggesting that corticosteroid drugs, such as prednisone, which are effective in DMD, are “re-synchronization” agents for muscle repair. In this way, he thinks, they act similarly to some of the body’s own hormones that synchronize sleep/wake cycles and other time-related events in the body.
His work will further study this phenomenon and explore its implications for development of drugs that offer the same benefits as corticosteroids with fewer side effects. He thinks there also may be a role for using the clock to schedule dosing of current drugs, timing their delivery to improve efficacy and reduce side effects.
“It is an exciting time for development of therapeutic approaches in Duchenne muscular dystrophy and other neuromuscular diseases,” Hoffman says, noting that the growing understanding of the biology of the dystrophin gene and the effects of the dystrophin protein’s loss in muscle is leading to novel therapeutic approaches, and the focus on moving those new approaches to clinical trials has sped up the development of promising therapies.
Funding for this MDA grant began Feb. 1, 2013.