Exploring new therapeutics for Duchenne muscular dystrophy and related cardiomyopathy

Rare Disease and Orphan Drugs Journal, Journal Year: 2025, Volume and Issue: 5(2)

Published: March 26, 2025

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

Language: Английский

Identification of VDAC1 as a mitochondria-related target of Duchenne muscular dystrophy based on bioinformatics analysis and in vitro experiments

International Immunopharmacology, Journal Year: 2025, Volume and Issue: 158, P. 114836 - 114836

Published: May 12, 2025

Language: Английский

Mechanisms of Chimeric Cell Therapy in Duchenne Muscular Dystrophy

Biomedicines, Journal Year: 2024, Volume and Issue: 12(9), P. 1996 - 1996

Published: Sept. 2, 2024

Despite scientific efforts, there is no cure for Duchenne muscular dystrophy (DMD), a lethal, progressive, X-linked genetic disorder caused by mutations in the dystrophin gene. DMD leads to cardiac and skeletal muscle weakness, resulting premature death due cardio-pulmonary complications. We have developed Dystrophin Expressing Chimeric (DEC) cell therapy, DT-DEC01, fusing human myoblasts from healthy donors patients. Preclinical studies on DEC cells showed increased expression improved cardiac, pulmonary, function after intraosseous administration. Our clinical study confirmed safety efficacy of DT-DEC01 therapy up 24 months post-administration. In this study, we conducted vitro assays test composition potency assessing chimerism level presence dystrophin, desmin, myosin heavy chain. Myoblast fusion resulted transfer donor mitochondria creation chimeric within DT-DEC01. The Pappenheim assay myotube formation final product. This highlights unique properties their relevance treatment mechanisms.

Language: Английский