Development of an orally available therapeutic drug to address the root cause of progressive muscle loss in Duchenne muscular dystrophy


Pre-Clinical Research

Poster Number: 131


Ryan Mitchell, PhD, Satellos Bioscience, Sridhar Narayan, PhD, MBA, Satellos Bioscience Inc, Frank Gleeson, MBA, Satellos Bioscience Inc, Michael Rudnicki, PhD, Satellos Bioscience Inc

Muscle stem cells, first characterized by Satellos founder Dr. Michael Rudnicki , represent a subpopulation of satellite cells located in a specialized niche beneath the basal lamina of myofibers. Muscle stem cells mediate the growth and regeneration of skeletal muscle through apical-basal oriented cell divisions which give rise to Pax7+/Myf5+ progenitor muscle cells. In a landmark paper , the Rudnicki lab demonstrated that the dystrophin protein is expressed in activated muscle stem cells where it is required for establishing apical-basal polarity. Absent the dystrophin protein, muscle stem cells cannot produce enough progenitor cells to keep up with ongoing muscle damage in Duchenne muscular dystrophy. We contend that impaired regeneration is the true root cause of the progressive muscle loss in Duchenne. Satellos is focused on developing therapeutic drugs which will restore the body’s innate regenerative capacity, offering new hope to people living with Duchenne. We have identified multiple regulatory pathways with the potential to affect polarity in muscle stem cells . Our lead drug program for Duchenne targets a specific enzyme in the EGFR pathway that, we have found, affords robust restoration of progenitor production and results in enhanced regeneration, improved muscle quality, and increased functional outputs across multiple preclinical models of Duchenne. Here we present our most up to date preclinical data in support of our novel therapeutic approach.