Nicotinamide Riboside Improves Muscle Function in Duchenne Muscular Dystrophy: Preclinical Findings

Synopsis

Neuromuscular diseases such as Duchenne muscular dystrophy (DMD) arise from genetic mutations that cause progressive muscle weakness and degeneration. This study identifies nicotinamide adenine dinucleotide (NAD+) depletion as a key metabolic hallmark contributing to muscle deterioration. Researchers found that in healthy mice, genes involved in mitochondrial biogenesis, muscle structure (dystrophin-sarcoglycan complex), and NAD+ biosynthesis were closely linked—suggesting NAD+ plays a protective role in muscle integrity. In both human DMD patients and mouse models, muscles showed reduced NAD+ levels, elevated PARP activity, and increased NNMT expression, indicating excessive NAD+ consumption and metabolic stress. Supplementing nicotinamide riboside (NR), a vitamin B3–derived NAD+ precursor, restored NAD+ levels in DMD mouse models, improving muscle strength, heart function, and mitochondrial health, while reducing inflammation and fibrosis. These findings suggest that NAD+ repletion through NR supplementation could represent a promising therapeutic strategy for muscular dystrophies and other neuromuscular degenerative diseases characterized by mitochondrial dysfunction and NAD+ depletion.

Journal

Science Translational Medicine