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Evolving Therapeutic Options for the Treatment of Duchenne Muscular Dystrophy

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Abstract

Duchenne muscular dystrophy (DMD) is the most common childhood form of muscular dystrophy. It is caused by mutations in the DMD gene, leading to reduced or absent expression of the dystrophin protein. Clinically, this results in loss of ambulation, cardiomyopathy, respiratory failure, and eventually death. In the past decades, the use of corticosteroids has slowed down the disease progression. More recently, the development of genetically mediated therapies has emerged as the most promising treatment for DMD. These strategies include exon skipping with antisense oligonucleotides, gene replacement therapy with adeno-associated virus, and gene editing with CRISPR (clustered regularly interspaced short palindromic repeats) technology. In this review, we highlight the most up-to-date therapeutic progresses in the field, with emphasis on past and recent experiences, as well as the latest clinical results of DMD micro-dystrophin gene therapy. Additionally, we discuss the lessons learned along the way and the challenges encountered, all of which have helped advance the field, with the potential to finally alleviate such a devastating disease.

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Acknowledgements

The micro-dystrophin gene therapy clinical trials have been done with Sarepta Therapeutics as the Industry Sponsor.

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  1. Center for Gene Therapy, Department of Pediatrics, Abigail Wexner Research Institute, Nationwide Children’s Hospital, Ohio State University, Columbus, OH, 43205, USA

    Eleonora S. D’Ambrosio & Jerry R. Mendell

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D’Ambrosio, E.S., Mendell, J.R. Evolving Therapeutic Options for the Treatment of Duchenne Muscular Dystrophy. Neurotherapeutics 20, 1669–1681 (2023). https://doi.org/10.1007/s13311-023-01423-y

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