Vamorolone improves Becker muscular dystrophy and increases dystrophin protein in model mice

Document Type

Journal Article

Publication Date

7-21-2023

Journal

iScience

Volume

26

Issue

7

DOI

10.1016/j.isci.2023.107161

Keywords

Biological sciences; Neuroscience; Pharmacology

Abstract

There is no approved therapy for Becker muscular dystrophy (BMD), a genetic muscle disease caused by in-frame dystrophin deletions. We previously developed the dissociative corticosteroid vamorolone for treatment of the allelic, dystrophin-null disease Duchenne muscular dystrophy. We hypothesize vamorolone can treat BMD by safely reducing inflammatory signaling in muscle and through a novel mechanism of increasing dystrophin protein via suppression of dystrophin-targeting miRNAs. Here, we test this in the mouse model of BMD. Daily oral treatment with vamorolone or prednisolone improves grip strength and hang time phenotypes. Both drugs reduce myofiber size and decrease the percentage of centrally nucleated fibers. Vamorolone shows improved safety versus prednisolone by avoiding or reducing key side effects to behavior and growth. Intriguingly, vamorolone increases dystrophin protein in both heart and skeletal muscle. These data indicate that vamorolone, nearing approval for Duchenne, shows efficacy in mice and therefore warrants clinical investigation in BMD.

Department

Genomics and Precision Medicine

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