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Abstract

Background/Objectives: Duchenne muscular dystrophy (DMD) is a fatal, progressive neuromuscular disorder caused by mutations in the dystrophin gene, leading to the absence of functional dystrophin protein. As the largest gene in the human genome, the DMD locus is highly susceptible to mutations, contributing to a prevalence of approximately 1 in 3800–6300 live male births worldwide. This review aims to provide a comprehensive and critical synthesis of current and emerging therapeutic strategies for DMD.

Methods: We conducted a narrative review of the literature, integrating findings from clinical trials, regulatory approvals, and preclinical studies. We categorized therapeutic approaches into mutation-agnostic and mutation-specific strategies, with emphasis on the mechanism of action, clinical progress, and translational limitations.

Results: Current standards of care, including corticosteroids and supportive interventions, remain foundational in disease management. Mutation-specific approaches such as exon skipping and adeno-associated virus (AAV)-mediated gene replacement can restore dystrophin expression, although clinical benefit remains variable and is influenced by factors such as mutation type, delivery efficiency, and durability. Emerging genome editing strategies offer the potential for permanent correction but face significant challenges related to delivery, safety, and scalability. Emerging mutation-agnostic therapies targeting inflammation, fibrosis, and membrane instability provide broader applicability but do not directly address the underlying genetic defect. Across modalities, key limitations include modest functional outcomes, safety concerns, and variability in clinical trial endpoints.

Conclusions: The DMD therapeutic landscape is rapidly evolving, and future progress will likely depend on optimizing delivery platforms, improving durability, and integrating combination strategies to address the multifaceted nature of disease progression.

Document Type

Article

Publication Date

2026

Notes/Citation Information

© 2026 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license.

Digital Object Identifier (DOI)

https://doi.org/10.3390/genes17050533

Funding Information

This work was supported by the Office of the Assistant Secretary of Defense for Health Affairs through the Duchenne Muscular Dystrophy Research Program of the Congressionally Directed Research Program under Award No. HT9425-23-1-0940. The opinions, interpretations, conclusions, and recommendations are those of the authors and are not necessarily endorsed by the Department of Defense.

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