Beyond muscle: Delivering RNA therapeutics to the CNS in Duchenne muscular dystrophy.

Abstract

Duchenne Muscular Dystrophy (DMD) is a severe genetic disorder characterized by progressive muscle degeneration due to mutations in the dystrophin gene. In addition to the well-known musculoskeletal, cardiac, and respiratory symptoms, DMD also involves significant central nervous system (CNS) manifestations, including cognitive, behavioral, and emotional deficits that profoundly affect patient quality of life. Despite advances in RNA-based therapies targeting muscle symptoms, CNS manifestations remain largely untreated. Preclinical studies in animal models have shown promising results in addressing these deficits through CNS-targeted delivery of antisense oligonucleotides, highlighting the potential of intrathecal and next-generation systemic delivery methods. This review explores the latest advancements in RNA therapeutics for DMD, focusing on overcoming the challenges of CNS delivery to address both muscular and neurological symptoms.