We developed a primary high throughput screen (HTS) and a secondary hit validation assay to identify small molecules for muscular dystrophy type I (DM1). This novel strategy allowed the identification of a highly potent and selective small molecule (MDI16 that effectively and specifically rescues DM1 pathology in both patient myoblasts and in mouse models that demonstrate DM1 pathology in skeletal muscle. As CNS pathology is a very serious feature of DM1 we propose to test and optimize blood brain barrier permeability and CNS efficacy of leads to accelerate the delivery of a rational therapy for DM1.