2073-440913142024Jul09CellsCardiomyopathy in Duchenne Muscular Dystrophy and the Potential for Mitochondrial Therapeutics to Improve Treatment Response.116810.3390/cells13141168Duchenne muscular dystrophy (DMD) is a progressive neuromuscular disease caused by mutations to the dystrophin gene, resulting in deficiency of dystrophin protein, loss of myofiber integrity in skeletal and cardiac muscle, and eventual cell death and replacement with fibrotic tissue. Pathologic cardiac manifestations occur in nearly every DMD patient, with the development of cardiomyopathy-the leading cause of death-inevitable by adulthood. As early cardiac abnormalities are difficult to detect, timely diagnosis and appropriate treatment modalities remain a challenge. There is no cure for DMD; treatment is aimed at delaying disease progression and alleviating symptoms. A comprehensive understanding of the pathophysiological mechanisms is crucial to the development of targeted treatments. While established hypotheses of underlying mechanisms include sarcolemmal weakening, upregulation of pro-inflammatory cytokines, and perturbed ion homeostasis, mitochondrial dysfunction is thought to be a potential key contributor. Several experimental compounds targeting the skeletal muscle pathology of DMD are in development, but the effects of such agents on cardiac function remain unclear. The synergistic integration of small molecule- and gene-target-based drugs with metabolic-, immune-, or ion balance-enhancing compounds into a combinatorial therapy offers potential for treating dystrophin deficiency-induced cardiomyopathy, making it crucial to understand the underlying mechanisms driving the disorder.GandhiShivamSSchool of Kinesiology and Health Science, Muscle Health Research Centre, York University, Toronto, ON M3J 1P3, Canada.SweeneyH LeeHLDepartment of Pharmacology and Therapeutics, University of Florida, Gainesville, FL 32610, USA.Myology Institute, University of Florida, Gainesville, FL 32610, USA.HartCora CCCDepartment of Pharmacology and Therapeutics, University of Florida, Gainesville, FL 32610, USA.Myology Institute, University of Florida, Gainesville, FL 32610, USA.HanRenzhiR0000-0002-8202-9186Department of Pediatrics, Herman B Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, IN 46202, USA.PerryChristopher G RCGRSchool of Kinesiology and Health Science, Muscle Health Research Centre, York University, Toronto, ON M3J 1P3, Canada.engR01 HL170260HLNHLBI NIH HHSUnited StatesN/AStealth BioTherapeutics (United States)Journal ArticleReviewResearch Support, Non-U.S. Gov't20240709