Histone deacetylase 6 inhibition promotes microtubule acetylation and facilitates autophagosome-lysosome fusion in dystrophin-deficient mdx mice.

Aim: Duchenne muscular dystrophy is a progressive muscle-wasting disease caused by mutations in the dystrophin gene. Despite progress in dystrophin-targeted gene therapies, it is still a fatal disease requiring novel therapeutics that can be used synergistically or alternatively to emerging gene therapy. Defective autophagy and disorganized microtubule networks contribute to dystrophic pathogenesis, yet the mechanisms by which microtubule alterations regulate autophagy remain elusive.

Exploring novel natural compound-based therapies for Duchenne muscular dystrophy management: insights from network pharmacology, QSAR modeling, molecular dynamics, and free energy calculations.

Muscular dystrophies encompass a heterogeneous group of rare neuromuscular diseases characterized by progressive muscle degeneration and weakness. Among these, Duchenne muscular dystrophy (DMD) stands out as one of the most severe forms. The present study employs an integrative approach combining network pharmacology, quantitative structure-activity relationship (QSAR) modeling, molecular dynamics (MD) simulations, and free energy calculations to identify potential therapeutic targets and natural compounds for DMD.

Novel gene therapies for sickle cell disease, Duchenne muscular dystrophy, and hemophilia A.

This article discusses novel genetic therapies for sickle cell disease, Duchenne muscular dystrophy, and hemophilia A. Gene therapies have the potential to deliver more targeted and effective approaches to treatment, especially for rare diseases for which the availability of approved therapies is limited. This article describes the first FDA-approved CRISPR/Cas9 treatment and the treatment protocols, indications, warnings, precautions, cost, and contraindications of four novel genetic therapies.

In Silico Structural Prediction for the Generation of Novel Performant Midi-Dystrophins Based on Intein-Mediated Dual AAV Approach.

Duchenne Muscular Dystrophy (DMD) is a pediatric disorder characterized by progressive muscle degeneration and premature death, and has no current cure. The current, most promising therapeutic avenue is based on gene replacement mediated by adeno-associated viruses (AAVs) using a shortened, but still functional, version of dystrophin, known as micro-dystrophin (µDys), to fit AAV capacity. The limited improvements observed in clinical trials suggest a sub-optimal performance of µDys in the human context that could be due to the lack of key domains in the protein.

Macrophages in the Context of Muscle Regeneration and Duchenne Muscular Dystrophy.

Macrophages are essential to muscle regeneration, as they regulate inflammation, carry out phagocytosis, and facilitate tissue repair. These cells exhibit phenotypic switching from pro-inflammatory (M1) to anti-inflammatory (M2) states during muscle repair, influencing myoblast proliferation, differentiation, and myofiber formation. In Duchenne Muscular Dystrophy (DMD), asynchronous muscle injuries disrupt the normal temporal stages of regeneration, leading to fibrosis and failed regeneration.

Effect of Oral Zinc Supplementation on Phase Angle and Bioelectrical Impedance Vector Analysis in Duchenne Muscular Dystrophy: A Non-Randomized Clinical Trial.

Zinc plays a crucial role in cell structure and functionality. Neurodegenerative Duchenne muscular dystrophy (DMD) alters muscle membrane structure, leading to a loss of muscle mass and strength. The objective of this study was to evaluate the changes in phase angle (PA) and bioelectrical impedance vector analysis (BIVA) results in patients with DMD after oral zinc supplementation.

Safety and efficacy of viltolarsen in ambulatory and nonambulatory males with Duchenne muscular dystrophy.

Duchenne muscular dystrophy (DMD) is an X-linked recessive disease characterized by mutations in the dystrophin gene, causing motor and pulmonary function decline. Viltolarsen is indicated for patients with dystrophin gene mutations amenable to exon 53 skipping. Here, we report safety, motor function, and the first pulmonary function results from the open-label, phase II Galactic53 trial of viltolarsen (NCT04956289).

Antisense oligonucleotides and their applications in rare neurological diseases.

Rare diseases affect almost 500 million people globally, predominantly impacting children and often leading to significantly impaired quality of life and high treatment costs. While significant contributions have been made to develop effective treatments for those with rare diseases, more rapid drug discovery strategies are needed. Therapeutic antisense oligonucleotides can modulate target gene expression with high specificity through various mechanisms determined by base sequences and chemical modifications; and have shown efficacy in clinical trials for a few rare neurological conditions.

A model-informed clinical trial simulation tool with a graphical user interface for Duchenne muscular dystrophy.

Quantitative model-based clinical trial simulation tools play a critical role in informing study designs through simulation before actual execution. These tools help drug developers explore various trial scenarios in silico to select a clinical trial design to detect therapeutic effects more efficiently, therefore reducing time, expense, and participants' burden. To increase the usability of the tools, user-friendly and interactive platforms should be developed to navigate various simulation scenarios.

Clinical and Molecular Profile of Duchenne Muscular Dystrophy (DMD): Case-Record Analysis From Uttar Pradesh, India.

Objective: To assess the clinical and molecular profile of patients with Duchenne Muscular Dystrophy (DMD) presenting to a tertiary center in Eastern Region of Uttar Pradesh, India.

Methods: In this retrospective study, case records of all patients diagnosed as DMD were analyzed to ascertain the clinical phenotype and molecular profile. Multiplex polymerase chain reaction (mPCR) technique, Multiplex Ligation Dependent Probe Amplification (MLPA) and Next Generation Sequencing (NGS) were used for establishing the molecular diagnosis.