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

Karim Azzag¹, Alessandro Magli², James Kiley¹, Darin Sumstad³, Diane Kadidlo³, Sarah B Crist¹, Beverly Norris⁴, Aaron Ahlquist¹, Laura L Hocum Stone⁵, John Everett⁶, Jill Shappa Faustich⁵, Davis Seelig⁷, Parthasarathy Rangarajan⁵, Hyunkee Kim¹, Craig Flory⁴, Frederic Bushman⁶, Sabarinathan Ramachandran⁸, Peter B Kang⁹, Robert J Schumacher⁴, John E Wagner¹⁰, Michael Kyba¹¹, Melanie L Graham¹², David H McKenna¹³, Rita C R Perlingeiro¹⁴

Affiliations

¹ Lillehei Heart Institute, Department of Medicine, University of Minnesota, Minneapolis, MN 55455, USA.
² Lillehei Heart Institute, Department of Medicine, University of Minnesota, Minneapolis, MN 55455, USA; Stem Cell Institute, University of Minnesota, Minneapolis, MN 55455, USA.
³ Molecular and Cellular Therapeutics, University of Minnesota, St. Paul, MN 55108, USA.
⁴ Center for Translational Medicine, University of Minnesota, Minneapolis, MN 55455, USA.
⁵ Department of Surgery, University of Minnesota, Minneapolis, MN 55455, USA.
⁶ Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
⁷ Department of Veterinary Clinical Sciences, University of Minnesota, St. Paul, MN 55108, USA; Department of Comparative Pathology Shared Resource, Masonic Cancer Center, University of Minnesota, Minneapolis, MN 55455, USA.
⁸ Stem Cell Institute, University of Minnesota, Minneapolis, MN 55455, USA; Department of Surgery, University of Minnesota, Minneapolis, MN 55455, USA.
⁹ Greg Marzolf Jr. Muscular Dystrophy Center, University of Minnesota, Minneapolis, MN 55455, USA; Department of Neurology, University of Minnesota, Minneapolis, MN 55455, USA.
¹⁰ Stem Cell Institute, University of Minnesota, Minneapolis, MN 55455, USA; Department of Pediatrics, University of Minnesota, Minneapolis, MN 55455, USA.
¹¹ Stem Cell Institute, University of Minnesota, Minneapolis, MN 55455, USA; Greg Marzolf Jr. Muscular Dystrophy Center, University of Minnesota, Minneapolis, MN 55455, USA; Department of Pediatrics, University of Minnesota, Minneapolis, MN 55455, USA.
¹² Department of Surgery, University of Minnesota, Minneapolis, MN 55455, USA; Department of Veterinary Population Medicine, University of Minnesota, St. Paul, MN 55108, USA.
¹³ Stem Cell Institute, University of Minnesota, Minneapolis, MN 55455, USA; Molecular and Cellular Therapeutics, University of Minnesota, St. Paul, MN 55108, USA.
¹⁴ Lillehei Heart Institute, Department of Medicine, University of Minnesota, Minneapolis, MN 55455, USA; Stem Cell Institute, University of Minnesota, Minneapolis, MN 55455, USA; Greg Marzolf Jr. Muscular Dystrophy Center, University of Minnesota, Minneapolis, MN 55455, USA. Electronic address: perli032@umn.edu.

PMID: 40682272
PMCID: PMC12338975 (available on 2026-07-17)
DOI: 10.1016/j.ymthe.2025.07.007

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

Karim Azzag et al. Mol Ther. 2025.

. 2025 Oct 1;33(10):5099-5117.

doi: 10.1016/j.ymthe.2025.07.007. Epub 2025 Jul 17.

Authors

Affiliations

¹ Lillehei Heart Institute, Department of Medicine, University of Minnesota, Minneapolis, MN 55455, USA.
² Lillehei Heart Institute, Department of Medicine, University of Minnesota, Minneapolis, MN 55455, USA; Stem Cell Institute, University of Minnesota, Minneapolis, MN 55455, USA.
³ Molecular and Cellular Therapeutics, University of Minnesota, St. Paul, MN 55108, USA.
⁴ Center for Translational Medicine, University of Minnesota, Minneapolis, MN 55455, USA.
⁵ Department of Surgery, University of Minnesota, Minneapolis, MN 55455, USA.
⁶ Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
⁷ Department of Veterinary Clinical Sciences, University of Minnesota, St. Paul, MN 55108, USA; Department of Comparative Pathology Shared Resource, Masonic Cancer Center, University of Minnesota, Minneapolis, MN 55455, USA.
⁸ Stem Cell Institute, University of Minnesota, Minneapolis, MN 55455, USA; Department of Surgery, University of Minnesota, Minneapolis, MN 55455, USA.
⁹ Greg Marzolf Jr. Muscular Dystrophy Center, University of Minnesota, Minneapolis, MN 55455, USA; Department of Neurology, University of Minnesota, Minneapolis, MN 55455, USA.
¹⁰ Stem Cell Institute, University of Minnesota, Minneapolis, MN 55455, USA; Department of Pediatrics, University of Minnesota, Minneapolis, MN 55455, USA.
¹¹ Stem Cell Institute, University of Minnesota, Minneapolis, MN 55455, USA; Greg Marzolf Jr. Muscular Dystrophy Center, University of Minnesota, Minneapolis, MN 55455, USA; Department of Pediatrics, University of Minnesota, Minneapolis, MN 55455, USA.
¹² Department of Surgery, University of Minnesota, Minneapolis, MN 55455, USA; Department of Veterinary Population Medicine, University of Minnesota, St. Paul, MN 55108, USA.
¹³ Stem Cell Institute, University of Minnesota, Minneapolis, MN 55455, USA; Molecular and Cellular Therapeutics, University of Minnesota, St. Paul, MN 55108, USA.
¹⁴ Lillehei Heart Institute, Department of Medicine, University of Minnesota, Minneapolis, MN 55455, USA; Stem Cell Institute, University of Minnesota, Minneapolis, MN 55455, USA; Greg Marzolf Jr. Muscular Dystrophy Center, University of Minnesota, Minneapolis, MN 55455, USA. Electronic address: perli032@umn.edu.

PMID: 40682272
PMCID: PMC12338975 (available on 2026-07-17)
DOI: 10.1016/j.ymthe.2025.07.007

Abstract

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.

Keywords: CGMP product; GLP preclinical studies; MyoPAXon; efficacy; iPS cells; muscle regeneration; muscular dystrophy; myogenic progenitors; non-human primates; safety.

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Conflict of interest statement

Declaration of interests R.C.R.P. and M.K. are cofounders and hold equity in Myogenica. A.M. is currently a Sanofi employee.

References

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

Affiliations

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

Authors

Affiliations

Abstract

Conflict of interest statement

References

MeSH terms

Substances

Grants and funding

LinkOut - more resources

Full Text Sources

Medical