A Potential Beta-hydroxybutyrate Therapy for Duchenne Muscular Dystrophy in Disease Models

Abstract

Duchenne muscular dystrophy (DMD) is a common and lethal muscular degenerative disorder caused by mutations in the Dystrophin gene. Patients with DMD suffer progressive motor and respiratory decline over time and exhibit mitochondria defects at the cellular level, contributing to their reduced life expectancy. Despite extensive efforts, effective treatments for DMD remain unavailable. This study aims to explore a dietary approach to treat DMD, by precisely utilizing ketone bodies, an alternative fuel and signaling molecule for the mitochondria. As the experimental design, beta-hydroxybutyrate (BHB), the ketone body that is most abundant and stable in mammals, was supplemented in the drinking water of DMD disease model mice (mdx mice) as well as wild type mice. The results show that exogenous BHB supplementation in mdx mice led to significant decreases in plasma creatine kinase (CK) levels compared to chow-fed mdx mice, indicating mitigation of muscle damages. Functional tests also show that BHB improved muscle strength and endurance in mdx mice, while histological analyses revealed muscle health restoration, evidenced in uniform fiber diameter. BHB supplementation did not adversely affect the growth and overall health in either wild type or mdx mice. These findings may provide the proof-of-principle evidence for the use of BHB as a potential dietary approach for DMD treatment.