Madhurima Saha, Skylar A Rizzo, Manashwi Ramanathan, Rylie M Hightower, Katherine E Santostefano, Naohiro Terada, Richard S Finkel, Jonathan S Berg, Nizar Chahin, Christina A Pacak, Richard E Wagner, Matthew S Alexander, Isabelle Draper, Peter B Kang
MEGF10 myopathy is a rare inherited muscle disease that is named after the causative gene, MEGF10. The classic phenotype, early onset myopathy, areflexia, respiratory distress and dysphagia, is severe and immediately life-threatening. There are no disease-modifying therapies. We performed a small molecule screen and follow-up studies to seek a novel therapy. A primary in vitro drug screen assessed cellular proliferation patterns in Megf10-deficient myoblasts. Secondary evaluations were performed on primary screen hits using myoblasts derived from Megf10-/- mice, induced pluripotent stem cell-derived myoblasts from MEGF10 myopathy patients, mutant Drosophila that are deficient in the homologue of MEGF10 (Drpr) and megf10 mutant zebrafish...
July 15, 2019: Human Molecular Genetics