Abstract
Duchenne muscular dystrophy (DMD) is a devastating disease featuring skeletal muscle wasting, respiratory insufficiency, and cardiomyopathy. Historically, respiratory failure has been the leading cause of mortality in DMD, but recent improvements in symptomatic respiratory management have extended the life expectancy of DMD patients. With increased longevity, the clinical relevance of heart disease in DMD is growing, as virtually all DMD patients over 18 year of age display signs of cardiomyopathy. This review will focus on the pathophysiological basis of DMD in the heart and discuss the therapeutic approaches currently in use and those in development to treat dystrophic cardiomyopathy. The first section will describe the aspects of the DMD that result in the loss of cardiac tissue and accumulation of fibrosis. The second section will discuss cardiac small molecule therapies currently used to treat heart disease in DMD, with a focus on the evidence supporting the use of each drug in dystrophic patients. The final section will outline the strengths and limitations of approaches directed at correcting the genetic defect through dystrophin gene replacement, modification, or repair. There are several new and promising therapeutic approaches that may protect the dystrophic heart, but their limitations suggest that future management of dystrophic cardiomyopathy may benefit from combining gene-targeted therapies with small molecule therapies. Understanding the mechanistic basis of dystrophic heart disease and the effects of current and emerging therapies will be critical for their success in the treatment of patients with DMD.
Highlights
Muscular dystrophies are a diverse group of rare genetic diseases characterized by progressive skeletal muscle wasting
As the dystrophic process progresses, these deficits in mitochondrial morphology become more apparent, reflecting that mitochondrial dysfunction is potentially both a cause and effect of the dystrophic process [76]. These findings demonstrate that mitochondrial energy production is limited early in the disease process, well before significant fibrosis or declines in contractile function are evident
Just over 30 years since the discovery of the protein dystrophin, and nearly two centuries after the first descriptions of the devastating disease precipitated by its loss, efforts to understand and correct the underlying pathology of Duchenne muscular dystrophy (DMD) are advancing by leaps and bounds
Summary
Muscular dystrophies are a diverse group of rare genetic diseases characterized by progressive skeletal muscle wasting. Some of the more devastating muscular dystrophies are those that develop due to the absence of components of the dystrophin-glycoprotein complex (DGC), resulting in compromised sarcolemmal integrity in skeletal muscle and the heart. These forms of muscular dystrophy feature both skeletal muscle wasting and marked cardiomyopathy. In the 21st century, heart failure is a leading cause of death in DMD, with many patients reaching adolescence or adulthood and displaying symptoms of dystrophic heart disease without receiving cardiac therapy [2,4]. Given the critical role of the heart in the disease process and quality of life, this review will focus on current understanding of cardiac involvement in DMD and detail how current and future therapies may delay or prevent the onset of heart failure in DMD patients
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
