We will evaluate human induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) harboring the DMD mutation del46-48 to study the effects gene therapy using mini-dystrophin. On a molecular level, this genetic variant disrupts dystrophin and leads to a severe DMD like phenotype with associated cardiomyopathy. We expect this mutation to disrupt the dystrophin complex. We propose using traditional 2D cell culture and 3D engineered heart tissue (EHT) technology, with iPSC-CMs, to define at the molecular level changes in dystrophin complex and utrophin expression at baseline and in response to micro-dystrophin gene therapy. Dystrophin localizes to the cell membrane in the EHT format, while it does not localize properly in conventional 2D culture. We will employ physiologic mechanical stress to assess the functional efficacy of micro-dystrophin gene therapy.
|Effective start/end date
|8/1/21 → 7/31/25
- Parent Project for Muscular Dystrophy Research, Inc. (PPMD AGMT 3-29-22)
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