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Duchenne muscular dystrophy (DMD) is the most common muscular disorder affecting children. It affects nearly 1 male birth over 5000. Oxidative stress is a pervasive feature in the pathogenesis of DMD. Recent work shows that the main generators of ROS are NADPH oxidases (NOX), suggesting that they are an early and promising target in DMD. In addition, skeletal muscles of mdx mice, a murine model of DMD, overexpress NOXes. We investigated the impact of diapocynin, a dimer of the NOX inhibitor apocynin, on the chronic disease phase of mdx mice. Treatment of these mice with diapocynin from 7 to 10 months of age resulted in decreased hypertrophy of several muscles, prevented force loss induced by tetanic and eccentric contractions, improved muscle and respiratory functions, decreased fibrosis of the diaphragm and positively regulated the expression of disease modifiers. These encouraging results ensure the potential role of diapocynin in future treatment strategies.
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http://dx.doi.org/10.1016/j.biopha.2024.116957 | DOI Listing |
J Neurochem
September 2025
Department of Biology and Biotechnologies "Charles Darwin", Sapienza University of Rome, Rome, Italy.
Patients with Duchenne muscular dystrophy (DMD) may experience neurobehavioral and cognitive concerns, including psychiatric symptoms, due to the absence of full-length dystrophin (Dp427), frequently accompanied by deficiencies in shorter isoforms. The lack of dystrophin affects neurophysiological processes from the uterine phase, impacting neural circuitry in brain regions such as the prefrontal cortex, hippocampus, and cerebellum. This leads to reduced inhibitory GABAergic transmission and altered hippocampal glutamatergic signaling.
View Article and Find Full Text PDFMol Ther Nucleic Acids
September 2025
Center for Genetic Medicine Research, Children's National Research Institute, Children's National Research and Innovation Campus, Children's National Hospital, Washington, DC 20012, USA.
Despite the proven safety of dystrophin-targeting phosphorodiamidate morpholino oligomer (PMO) therapy, poor delivery of the PMOs limit the efficacy of this dystrophin restoring gene therapy for Duchenne muscular dystrophy (DMD). Limited myogenesis and excessive fibrosis in DMD are pathological features that contribute to the poor efficacy of PMOs. We show that the severe DMD mouse model (D2-) not only replicates these pathological features of DMD but also mirrors the resulting PMO-mediated dystrophin restoration deficit.
View Article and Find Full Text PDFbioRxiv
August 2025
Department of Pharmacology & Therapeutics and Myology Institute, University of Florida College of Medicine; Gainesville, FL USA.
Duchenne muscular dystrophy (DMD) is a lethal pediatric striated muscle disease caused by loss of dystrophin for which there is no cure. Cardiomyopathy is the leading cause of death amongst individuals with DMD, and effective therapeutics to treat DMD cardiomyopathy are a major unmet clinical need. This work investigated adeno-associated viral (AAV) gene therapy approaches to treat DMD cardiomyopathy by overexpression of the calcium binding proteins S100A1 and apoptosis repressor with caspase recruitment domains (ARC).
View Article and Find Full Text PDFFASEB J
July 2025
Division of Pediatric Cardiology, Department of Pediatrics, Children's Hospital of Richmond at Virginia Commonwealth University, Richmond, Virginia, USA.
Duchenne Muscular Dystrophy (DMD) is a progressive muscular degenerative disease that is recessively inherited through the X chromosome. Various mutations in the dystrophin gene lead to noticeable muscle weakness. The effects on skeletal and cardiac tissue result in progressive immobility and cardiac dysfunction, respectively.
View Article and Find Full Text PDFInt J Mol Sci
August 2025
Department of Neurology, Hospital for Special Surgery, 535 East 70th Street, New York, NY 10021, USA.
Monocytes/macrophages promote the repair of acutely injured muscle while contributing to dystrophic changes in chronically injured muscle in Duchenne muscular dystrophy (DMD) patients and animal models including and mice. To elucidate the molecular mechanisms underlying this functional difference, we compared the transcriptomes of intramuscular monocytes/macrophages from () uninjured muscles, acutely injured muscles, and dystrophic muscles, using single cell-based RNA sequencing (scRNA-seq) analysis. Our study identified multiple transcriptomically diverse monocyte/macrophage subclusters, which appear to be induced by the intramuscular microenvironment.
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