Preclinical quality, safety, and efficacy of a CGMP iPSC-derived myogenic progenitor product for the treatment of muscular dystrophies

Pluripotent stem cell (PSC)-derived therapies are in clinical trials of terminally differentiated or transiently required cell types, but to date no PSC-derived trial contributing tissue-specific stem cells or any PSC-based skeletal muscle regeneration trial has been approved. We describe a process in accordance with the Current Good Manufacturing Practice (CGMP) to generate large-scale cryopreserved PAX7-induced myogenic progenitors, which reconstitute both fibers and satellite cells, from PSCs. We subjected the clinical-grade cell product MyoPAXon to biodistribution, toxicity, and tumorigenicity studies in mice under Good Laboratory Practice conditions with no adverse effects and demonstrate long-term engraftment (>1 year) and efficacy in dystrophic mice. Transplantation of 37–60 million MyoPAXon cells into immunosuppressed non-human primates showed human contribution to muscle fibers and satellite cells, with no safety concerns. The US Food and Drug Administration has recently authorized this fully characterized off-the-shelf CGMP product for a first-in-human clinical trial in Duchenne muscular dystrophy, representing the first iPSC-derived tissue-specific stem cell therapy.