IPSC Therapy Designed to Deliver Full-length Dystrophin Gets Orphan Drug Designation for DMD


The therapy demonstrated an ability to repair injured muscle in mice models of Duchenne.

The FDA has granted orphan drug designation (ODD) to IPS HEART’s induced pluripotent stem (IPS) cell therapy GIVI-MPC for the potential treatment of Duchenne muscular dystrophy (DMD).1

“Given our successful pre-investigational new drug (IND) meeting with the FDA and our ongoing developmental efforts including Good Manufacturing Practice manufacturing, we believe that we will be the first IPS stem cell company with a disease modifying therapy to advance both drugs into human clinical trials whereby all current drugs largely only provide symptomatic relief,” Rauf Ashraf, chief executive officer, IPS HEART, said in a statement.1

GIVI-MPC previously showed efficacy in preclinical studies in mouse models in a paper published in Stem Cell Research & Therapy in 2021 by first author Wanling Xuan, PhD, assistant professor, Department of Pharmaceutical Science, Taneja College of Pharmacy, University of South Florida, and colleagues.2

“Human IPS cells and their derivatives offer important opportunities to treat a number of diseases. Here, we investigated whether givinostat, a histone deacetylase inhibitor, with muscle differentiation properties could reprogram hiPSCs into muscle progenitor cells (MPC) for DMD treatment,” Xuan and colleagues wrote.2

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The researchers found that givinostatdid successfully reprogram human IPS cells into MPCs with anti-oxidative, anti-inflammatory, and muscle gene-promoting properties which were able to effectively repair injured muscle and restoredystrophin in injured muscles of mice. Unlike other investigational gene and cell therapies in the indication that enable production of microdystrophin, GIVI-MPC is designed to be able to deliver full length dystrophin to muscles as well as regenerate muscles.

“In summary, we successfully generated highly expandable MPC from multiple hiPS cell lines using CHIR99021 and givinostat. Givinostat-induced MPC were highly proliferative and migratory in nature, and their transplantation resulted in a marked and impressive myoangiogenesis and restored dystrophin in injured TA muscle compared to the treatment with control MPC or adult human myoblasts. More importantly, they also replenished the satellite cell compartment,” Xuan and colleagues concluded.2 “It is concluded that hiPSCs reprogrammed into MPC by givinostat possessing anti-oxidative, anti-inflammatory, and muscle gene-promoting properties are an effective cellular source for the treatment of muscle injury and restoration of dystrophin in DMD muscle.”

In addition to GIVI-MPC, IPS-HEART has 2 other cell therapy candidates in its preclinical pipeline. These are ISX9-CPC, the company’s lead program being investigated to treat DMD-related cardiomyopathy and heart failure, and MIR373, being investigated to treat heart failure and fibrosis. ISX9-CPC was also granted ODD by the FDA in 2022.

1. FDA grants IPS HEART Orphan Drug Designation for GIVI-MPC for treatment of Duchenne muscular dystrophy. News release. IPS HEART. February 22, 2023. https://www.businesswire.com/news/home/20230222005684/en/FDA-grants-IPS-HEART-Orphan-Drug-Designation-for-GIVI-MPC-for-Treatment-of-Duchenne-Muscular-Dystrophy
2. Xuan W, Khan M, Asahraf M. Pluripotent stem cell-induced skeletal muscle progenitor cells with givinostat promote myoangiogenesis and restore dystrophin in injured Duchenne dystrophic muscle. Stem Cell Res Ther 12, 131 (2021). doi: 10.1186/s13287-021-02174-3
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