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The Science

Myogenica’s MyoPAXon platform is based on induced pluripotent stem cells (iPSCs) that express PAX7, which is only expressed in muscle stem cells or satellite cells.

The process begins with a GMP iPSC cell bank that is modified by a lentivirus to express PAX7. Following in vitro differentiation, the cells are purified using a cGMP compliant process using the proprietary CD54 cell marker. Further expansion of the CD54+ cells yields the MyoPAXon product which comprises homogeneous muscle stem cells. These cells are frozen and available for use in clinical studies for muscle diseases.

Muscle cross section showing donor-derived human muscle fibers expressing Dystrophin (white) in a transplanted Dystrophin-deficient mouse.

Transplanted MyoPAXon cells improve recipients’ existing muscle fibers, providing expression of missing proteins such as dystrophin and improving muscle function. MyoPAXon also creates a wellspring of muscle stem cells that generate new healthy muscle in response to future injury as well as to normal muscle tissue turnover with time. Based on a single treatment, MyoPAXon cells have demonstrated regenerative capacity at least 12 months later.

Our Progress

The MyoPAXon platform is currently late preclinical stage, with clinical studies in Duchenne muscular dystrophy to commence in 2024. The MyoPAXon development work has been funded by over $10M in grant funding over the course of 10 years.

Extensive animal efficacy with mouse-to-mouse and
human-to-mouse transplants

Re-injury studies and durability studies demonstrate regeneration and 1+ year efficacy

Pilot safety studies conducted, showing no toxicity & no carcinogenicity

Pre-IND meeting held with clear study plans established

Non-human primate (NHP) studies initiated

GLP toxicology studies completed

cGMP production of lentivirus;  cGMP production of master cell bank and MyoPAXon product in vitro and in vivo validation of cGMP MyoPAXon cells

    1. Azzag, K., Bosnakovski, D., Tungtur, S. et al. Transplantation of PSC-derived myogenic progenitors counteracts disease phenotypes in FSHD mice. npj Regen Med 7, 43 (2022). https://doi.org/10.1038/s41536-022-00249-0

    2. Dhoke N, Kim H, Selvaraj S, Oliveira NAJ, Azzag K, Tungtur S, Ortiz-Cordero C, Kiley J, Lu QL, Bang A, & Perlingeiro RCR, (2021), A universal gene correction approach for FKRP-associated dystroglycanopathies to enable autologous cell therapy. Cell Reports. 36(2):109360. PMCID: PMC8327854.

    3. Ortiz-Cordero C, Bincoletto, C, Dhoke N, Selvaraj S, Magli A, Zhou H, Kim D-H, Bang AG, & Perlingeiro RCR, (2021), Defective autophagy and increased apoptosis contribute toward the pathogenesis of FKRP-associated muscular dystrophies. Stem Cell Reports. 16(11):2752-2767. PMCID: PMC8581053.

    4. Ortiz-Cordero C, Magli A, Dhoke N, Kuebler T, Selvaraj S, Oliveira NA, Zhou H, Sham YY, Bang AG, & Perlingeiro RCR, (2021), NAD+ enhances ribitol and ribose rescue of α-dystroglycan functional glycosylation in human FKRP-mutant myotubes. Elife. 10:e65443. PMCID: PMC7924940.

    5. Kim H, Selvaraj S, Kiley J, Azzag K, Garay BI, & Perlingeiro RCR, (2021), Genomic safe harbor expression of PAX7 for the generation of engraftable myogenic progenitors. Stem Cell Reports. 16:10-19. PMCID: PMC7815936.

    6. Incitti T, Magli A, Jenkins J, Lin K, Yamamoto A and Perlingeiro RCR, (2020), Pluripotent stem cell-derived skeletal muscle fibers preferentially express oxidative myosin heavy-chain isoforms: new implications for Duchenne Muscular Dystrophy. Skeletal Muscle. 10(1):17. PMCID: PMC7268645.

    7. Azzag K, Ortiz-Cordero C, Oliveira NAJ, Magli A, Selvaraj S, Tungtur S, Upchurch W, Iaizzo PA, Lu QL and Perlingeiro RCR, (2020) Efficient Engraftment of Pluripotent Stem Cell-Derived Myogenic Progenitors in a Novel Immunodeficient Mouse Model of Limb Girdle Muscular Dystrophy 2I. Skeletal Muscle. 10(1):10. PMCID: PMC7175515.

    8. Selvaraj S, Mondragon-Gonzalez R, Xu B, Magli A, Kim H, Lainé J, Kiley J, McKee H, Rinaldi F, Aho J, Tabti N, Shen W, & Perlingeiro RCR, (2019) Screening identifies small molecules that enhance the maturation of human pluripotent stem cell-derived myotubes. eLIFE. 8. pii: e47970. PMCID: PMC6845233.

    9. Selvaraj S, Dhoke N, Kiley J, Aierdi AJM, Mondragon-Gonzalez R, Killeen G, Oliveira VKP, Tungtur S, Munain AL & Perlingeiro RCR, (2019) Gene Correction of Limb Girdle Muscular Dystrophy Type 2A Patient-Specific iPS Cells for the Development of Targeted Autologous Cell Therapy. Molecular Therapy. 27:2147-2157. PMCID: PMC6904833.

    10. Incitti, T, Magli A, Darabi R, Arpke RJ, Kyba M and Perlingeiro RCR. (2019) Pluripotent stem cell-derived myogenic progenitors remodel their molecular signature upon in vivo engraftment. Proc Natl Acad Sci U S A. 116:4346-4351. PMCID: PMC6410870.

    11. Mondragon-Gonzalez R and Perlingeiro RCR. (2018) Recapitulating muscle disease phenotypes with myotonic dystrophy iPS cells: a tool for disease modeling and drug discovery. Disease Models and Mechanism. 11(7); pii: dmm034728 PMCID: PMC6078411.

    12. Magli A, Incitti T, Kiley J, Swanson SA, Darabi R, Rinaldi F, Selvaraj S, Yamamoto A, Tolar J, Yuan C, Stewart R, Thomson JA, Perlingeiro RCR. (2017) PAX7 Targets, CD54, Integrin α9β1, and SDC2, Allow Isolation of Human ESC/iPSC-Derived Myogenic Progenitors. Cell Reports. 19:2867-2877. PMCID: PMC5528177.

    13. Kim J, Magli A, Chan SSK, Oliveira VKP, Wu J, Darabi R, Kyba M, & Perlingeiro RCR. (2017) Expansion and Purification Are Critical for the Therapeutic Application for Pluripotent Stem Cell-Derived Myogenic Progenitors. Stem Cell Reports. 9:12-22. PMCID: PMC5511038.

    14. Filareto A, Parker S, Darabi R, Borges L, Schaaf T, Mayerhofer T, Chamberlain JS, Ervasti JM, McIvor RS, Kyba M, & Perlingeiro RCR. (2013) An ex vivo gene therapy approach to treat muscular dystrophy using iPS cells. Nature Communications. 4:1549. PMCID: PMC3595133.

    15. Darabi R, Arpke RW, Irion S, Dimos JT, Kyba M, Grskovic M, & Perlingeiro RCR. (2012) Human ES- and iPS-derived myogenic progenitors restore dystrophin and improve contractility upon transplantation in dystrophic mice. Cell Stem Cell. 10:610-619. PMCID: PMC3348507.

    16. Filareto A, Darabi R, & Perlingeiro RCR. (2012) Engraftment of ES-Derived Myogenic Progenitors in a Severe Mouse Model of Muscular Dystrophy. Journal of Stem Cell Research and Therapy. 10:1. PMCID: PMC3593119.

    17. Darabi R, Pan W, Baik, J, Bosnakovski D, Kyba, M & Perlingeiro RCR. (2011) Functional myogenic engraftment from mouse iPS cells. Stem Cell Reviews and Reports. 7:948-957. PMCID: PMC4465364.

    18. Darabi R, Santos FNC, Filareto A, Pan W, Koene R, Rudnicki M, Kyba, M & Perlingeiro RCR. (2011) Assessment of the Myogenic Stem Cell Compartment Following Transplantation of Pax3/Pax7-Induced Embryonic Stem Cell-Derived Progenitors. Stem Cells. 29:777-790. PMCID: PMC3325545.

    19. Darabi R, Gehlbach K, Stull JT, Kamm KE, Kyba M & Perlingeiro RCR. (2008) Functional skeletal muscle regeneration from differentiating embryonic stem cells. Nature Medicine. 14:134-143. PMID: 18204461 (cover article).

    1. Kim H, & Perlingeiro RCR, (2022) Generation of human myogenic progenitors from pluripotentstem cells for in vivo regeneration. Cellular and Molecular Life Sciences. 8;79(8):406. doi: 10.1007/s00018-022-04434-8. PMCID: PMC9270264.

    2. Ortiz-Cordero C, Azzag K, & Perlingeiro RCR, (2021), Fukutin-Related Protein: from Pathology to Treatments. Trends in Cell Biology. 31:197-210. PMCID: PMC7815936. (cover article).

    3. Selvaraj S, Kyba M & Perlingeiro RCR, (2019) “Pluripotent Stem Cell-Based Therapeutics for Muscular Dystrophies” Trends in Molecular Medicine. 25:803-816. PMCID: PMC6721995. (cover article)

    4. Magli A and Perlingeiro RCR. (2017) Myogenic Progenitor Specification from Pluripotent Stem Cells. Invited Review for Seminars in Cell and Developmental Biology. 72:87-98. PMCID: PMC5528177.

    5. Rinaldi F, Zhang Y, Mondragon-Gonzalez R, Harvey J, & Perlingeiro RCR. (2016) Treatment with rGDF11 does not improve the dystrophic muscle pathology of mdx mice. Skeletal Muscle. 6:21. PMCID: PMC4906773.

    6. Magli A, Incitti T & Perlingeiro RCR. (2016) Myogenic Progenitors from Mouse Pluripotent Stem Cells for Muscle Regeneration. Methods Molecular Biology. 1460:191-208 PMID: 27492174.

    7. McCullagh KJA & Perlingeiro RCR. (2015) Coaxing stem cells for skeletal muscle repair. Advanced Drug Delivery Reviews. 84:198-207. PMCID: PMC4295015.

    8. Darabi R & Perlingeiro RCR. (2014) Derivation of Skeletal Myogenic Precursors from Human Pluripotent Stem Cells Using Conditional Expression of PAX7. Methods Molecular Biology. 1357:423-39. PMID: 25403466.

    9. Rinaldi F & Perlingeiro RCR. (2014) Stem Cells for Skeletal Muscle Regeneration: Therapeutic Potential and Roadblocks. Translational Research. 163:409-417. (invited review). PMCID: PMC3976768.

    10. Parker S & Perlingeiro RCR. (2013) Are we there yet? Navigating Roadblocks to iPS Therapy Translation. Regenerative Medicine. 8:389-291. PMID: 23826691.

    11. Darabi R & Perlingeiro RCR. (2013) A Perspective on the Potential of Human iPS Cell-Based Therapies for Muscular Dystrophies: Advancements So Far and Hurdles to Overcome. Journal of Stem Cell Research and Therapy. 3:2. PMCID: PMC3987665.

    12. Darabi R, Santos FNC & Perlingeiro RCR. (2008) The therapeutic potential of embryonic and adult stem cells for skeletal muscle regeneration. Stem Cell Reviews. 4:217-225 (invited review). PMID: 18607783.

    13. Darabi R & Perlingeiro RCR. (2008) Lineage-specific reprogramming as a strategy for cell therapy. Cell Cycle. 7:1732-1737 (invited review). PMID: 18583932.

  • April 2024: Duchenne UK and Parent Project Muscular Dystrophy Award $500,000 to fund Phase I/II MyoPAXon clinical trial