Multiomics Analyses of Steroid Drug Efficacy in Duchenne Muscular Dystrophy Cardiomyocytes

The recently approved drug vamorolone (Agamree) demonstrates comparable efficacy in motor function improvement to conventional glucocorticoids, such as prednisolone, but with markedly reduced side effects. Unlike many corticosteroids that increase blood volume and pressure, vamorolone exhibits cardioprotective properties.

However, molecular characterization of these effects has been challenging because traditional DMD models, including the mdx mouse, fail to manifest the cardiac disease phenotypes observed in patients. Here, we established a representative dystrophic cardiomyopathy model by differentiating DMD patient-derived induced pluripotent stem cells into cardiomyocytes (DMD-CMs). Compared with healthy control CMs, DMD-CMs exhibited downregulated transcriptional signatures resulting in extracellular matrix stability, cardiac action potential regulation and cytoskeletal integrity.