Systemic regeneration medicines for muscular dystrophy: progress and challenges in pro-regenerative drug development

Regenerative medicine has the potential to restore lost organ and tissue functions, and research on cell transplantation is steadily advancing toward clinical application. However, significant challenges remain in developing cell therapies for skeletal muscle, largely because the human body contains more than 600 individual muscles, making it impractical to treat all affected muscles through local transplantation alone. One strategy to overcome this limitation is to enhance the intrinsic regenerative capacity of muscle through various modalities; in this review, we define these approaches as pro-regenerative drugs. Histone deacetylase (HDAC) inhibitors provide a compelling example, demonstrating that stimulation of endogenous muscle regeneration can confer therapeutic benefits in the genetic disease Duchenne muscular dystrophy (DMD). This raises a fundamental question: why do pro-regenerative drugs provide durable benefits without Dystrophin restoration? This review summarizes the current status and importance of pro-regenerative drug development and discusses why sustained therapeutic effects can be achieved despite the lack of gene complementation. It also highlights key pathways that promote muscle regeneration as potential targets for future therapies.