Cardio-respiratory and phenotypicrescue of dystrophin/utrophin-deficientmice by combination therapy

ABSTRACT: Duchenne muscular dystrophy(DMD) is a systemic progressive muscular disease caused by frame-disrupting mutations in the DMD gene.Although exon-skipping antisense oligonucleotides(AOs) are clinically approved and can correct DMD, insufficient muscle delivery limits efficacy.If AO activity can be enhanced by safe dietary supplements,clinical trials for efficacy can be undertaken rapidly to benefit patients. We showed previously that intravenous glycine enhanced phosphorodiamidate morpholino oligomer(PMO) delivery to peripheral muscles in mdx mice.Here,we demonstrate that the combination of oral glycine and metformin with intravenous PMO enhances PMO activity, dystrophin restoration,extends lifespan, and improves body-wide function and phenotypic rescue of dystrophin/utrophin double knock-out

SUBMITTER: Prof. HAIFANG YIN 

PROVIDER: S-SCDT-EMBOR-2021-53955V1 | biostudies-other |

REPOSITORIES: biostudies-other