Gene expression data from DMD patient hiPSC-derived myoblasts treated with fenofibrate, ginsenoside Rd or DMSO

Drug development costs a significant amount of time and resources for new pharmaceutical drugs. However, the progress has been limited for orphan diseases such as Duchenne muscular dystrophy (DMD). By using human induced pluripotent stem cells (hiPSCs), here we show an exemplary drug screening campaign and the identification of two potential drugs effective in a DMD mouse model. We developed a DMD-hiPSC screening platform utilizing high-content imaging to identify hit compounds that enhance myogenic fusion abilities of patient-specific myoblasts. Among 1524 compounds (Johns Hopkins Clinical Compound library), two hit compounds restored in vitro fusion defects of DMD patient hiPSC-derived myoblasts. Transcriptional profiling revealed that the function of two hit compounds, ginsenoside Rd (natural product, ginseng extract) and fenofibrate (FDA-approved drug), are associated with FLT3 signaling and TGF-β signaling, respectively. The preclinical tests in mdx mice show that the treatment of the two hit compounds can ameliorate the skeletal muscle and behavioral phenotypes caused by DYSTROPHIN deficiency, suggesting therapeutic potential of these two compounds. Our study demonstrates the feasibility of early-stage drug development for rare diseases using symptom-relevant cells derived from patient-specific hiPSCs. Ginsenoside Rd (5μm), fenofibrate(8μm) or DMSO(solvent) were used to treat DMD patient (D2325) hiPSC-derived myoblasts for 24 hours in N2 medium without serum. 3 replicates of cells were harvests and processed further.