Muscle stem cells 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 polarized divisions which give rise to Pax7+/Myf5+ progenitor muscle cells. 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 causal for progressive muscle loss in Duchenne. Satellos is focused on developing therapeutics which restore the body’s innate regenerative capacity. We have identified multiple regulatory pathways with the potential to affect polarity in muscle stem cells. Our therapeutic approach targets specific enzymes that restore muscle stem cell polarity, progenitor production and result in enhanced regeneration, improved muscle quality, and increased functional outputs across multiple preclinical models of Duchenne, as well as MDC1A. Here we present our most up to date preclinical data in support of our novel therapeutic approach.