Exploring new therapeutics for Duchenne muscular dystrophy and related cardiomyopathy

Abstract

Duchenne muscular dystrophy (DMD) is a severe and progressively debilitating X-linked recessive disorder caused by mutations in the DMD gene, which encodes the dystrophin protein. This deficiency in dystrophin results in the progressive degeneration of both skeletal and cardiac muscles. Currently, there is no definitive cure for DMD, and treatment primarily aims to slow disease progression and manage symptoms. With the widespread application of respiratory support measures, DMD cardiomyopathy has emerged as the primary contributor to morbidity and mortality among DMD patients at present. There is an acute and pressing need to develop highly effective therapeutic strategies for treating DMD cardiomyopathy and to prevent the onset of heart failure. Various hypotheses have been proposed to explain the underlying mechanisms, including elevated levels of inflammatory cytokines, dysregulated HDAC activity, disruptions in ion balance, and mitochondrial dysfunction, which is also considered a potentially significant contributor. This review article aims to provide a comprehensive overview of various animal and human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) models on DMD and DMD cardiomyopathy. It also provides a summary of current advancements and ongoing efforts in the treatment of DMD and DMD-related cardiomyopathy, with a focus on innovative treatment modalities, such as mitochondria transplantation or targeting ion homeostasis. This underscores the dynamic and evolving nature of research dedicated to developing effective treatments for DMD and DMD cardiomyopathy.

Keywords

Duchenne muscular dystrophy / dystrophin / disease modeling / therapies / mitochondria

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