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Lead investigator

Collaborators & Co-Investigators

• Jean-Philip Lumb, PhD

Research Sites & Affiliations

• McGill University, Montreal, Quebec

Budget: $60,000

Disorders: Duchenne/Becker Muscular Dystrophy

Research Areas: Discover Novel Treatments & Therapies

Abstract: 

Duchenne muscular dystrophy (DMD) is a devastating muscle disease that affects ~1 in 3500 boys. DMD is caused by the absence of dystrophin protein in skeletal muscle, leading to chronic degeneration of muscle fibres. Muscle degeneration is initially counteracted by muscle stem cell (MuSC)-dependent muscle repair. However, chronic cycles of muscle degeneration and regeneration lead to MuSC exhaustion, which precedes the onset of progressive muscle degeneration. The resulting muscle weakness severely limits mobility and ultimately respiration of patients. until they succumb to disease in their third decade of life. Therapeutic strategies to increase or ‘expand’ MuSC populations hold significant promise to both alleviate and treat DMD. Expansion of donor MuSCs, both in culture and after engraftment, will facilitate cell-based therapies for DMD. Moreover, expansion of MuSCs in a DMD patient would be expected to prevent their exhaustion and further delay progression of disease. Our team has previously identified a major regulatory pathway for protein synthesis as a pharmacological target to expand MuSCs ex vivo. We showed that inhibition of this pathway with a small molecule, named ‘Sal003’, enables MuSC expansion. We will further improve the potency of Sal003 with the overall goal to expand MuSCs within skeletal muscle, with therapeutic implications for both cell based therapies, and new strategies that slow MuSC exhaustion in DMD and potentially other muscle disease.

Impact: