P254 Characterization of Short- and Long-Term Proteomic Response to the Fast Skeletal Myosin Inhibitor, EDG-5506, in Becker Muscular Dystrophy (BMD)

Neuromuscular Disorders 33 (2023) S66-S192 increasing dystrophin protein levels by suppressing DTM expression.Here we test this hypothesis in bmx mice, the first mouse model of BMD generated through deletion of murine exons 45 through 47.This mutation recreates a common BMD genotype which frequently presents clinically with more severe pathology with earlier onset of cardiomyopathy.We find daily oral treatment with vamorolone or prednisolone improves bmx strength through grip strength and hang time assays.Examining histopathology, both drugs reduce fiber size and decrease the percentage of centrally nucleated fibers.Importantly, vamorolone shows improved safety by avoiding the induction of anxiety behavior and stunted growth, key side effects that are apparent in prednisolone treatment.Intriguingly, we also find vamorolone increases dystrophin protein in both skeletal muscle and heart.This data indicates vamorolone, which is nearing approval for DMD after its initial development in mdx mice, also shows efficacy in a mouse model of BMD and therefore warrants clinical investigation in BMD patients.