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Duchenne muscular dystrophy

Nature Reviews Disease Primers volume 7, Article number: 13 (2021) Cite this article

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Abstract

Duchenne muscular dystrophy is a severe, progressive, muscle-wasting disease that leads to difficulties with movement and, eventually, to the need for assisted ventilation and premature death. The disease is caused by mutations in DMD (encoding dystrophin) that abolish the production of dystrophin in muscle. Muscles without dystrophin are more sensitive to damage, resulting in progressive loss of muscle tissue and function, in addition to cardiomyopathy. Recent studies have greatly deepened our understanding of the primary and secondary pathogenetic mechanisms. Guidelines for the multidisciplinary care for Duchenne muscular dystrophy that address obtaining a genetic diagnosis and managing the various aspects of the disease have been established. In addition, a number of therapies that aim to restore the missing dystrophin protein or address secondary pathology have received regulatory approval and many others are in clinical development.

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Fig. 1: Schematic depiction of DMD and dystrophin protein.
Fig. 2: Healthy muscle and DMD muscle histology.
Fig. 3: Dystrophin and binding partners.
Fig. 4: Diagnostic decision tree to confirm the genetic diagnosis of dystrophinopathies.
Fig. 5: Dystrophin-restoring approaches.

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Acknowledgements

The laboratory of A.A.-R. is part of the Duchenne Center Netherlands. Duchenne muscular dystrophy (DMD) research in the laboratory of A.A.-R. is currently supported by Duchenne Parent Project, Duchenne UK, Prinses Beatrix Spierfonds, Spieren voor Spieren and the EU Horizon 2020 project BIND. DMD research in the laboratory of D.D. is currently supported by the National Institutes of Health (NS90634, AR70517, AR69085), Jackson Freel DMD Research Fund, Jesse’s Journey: The Foundation for Gene and Cell Therapy, Parent Project Muscular Dystrophy (USA), Hope for Javier, Michael’s Cause, Ryan’s Quest, Pietro’s Fight, Duchenne UK, Ryan’s Rally, Team Joseph, Charley’s Fund, Cure Duchenne, and Jett Foundation. DMD research in the laboratory of N.G. is currently supported by Duchenne Parent Project, Rondou Fonds and Kan-Go! Fonds. We thank NIH NeuroBioBank for providing patient muscle tissue for histological studies. We thank N. Wasala (University of Missouri) and K. Zhang (University of Missouri) for their help in the preparation of Fig. 2.

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Authors and Affiliations

  1. Department of Molecular Microbiology and Immunology and Department of Neurology, School of Medicine; Department of Biomedical Sciences, College of Veterinary Medicine; Department of Biomedical, Biological & Chemical Engineering, College of Engineering, University of Missouri, Columbia, MO, USA

    Dongsheng Duan

  2. Department of Child Neurology, University Hospitals Leuven, Leuven, Belgium

    Nathalie Goemans

  3. National Center of Neurology and Psychiatry, Tokyo, Japan

    Shin’ichi Takeda

  4. Centro Clinico Nemo, Policlinico Gemelli, Rome, Italy

    Eugenio Mercuri

  5. Peadiatric Neurology, Catholic University, Rome, Italy

    Eugenio Mercuri

  6. Department of Human Genetics, Leiden University Medical Center, Leiden, The Netherlands

    Annemieke Aartsma-Rus

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  1. Dongsheng Duan
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Contributions

Introduction (A.A.-R.); Epidemiology (S.T. and A.A.-R.); Mechanisms/pathophysiology (D.D. and A.A.-R.); Diagnosis, screening and prevention (A.A.-R. and N.G.); Management (N.G., E.M. and S.T.); Quality of life (N.G. and E.M.); Outlook (A.A.-R. and D.D.); Overview of Primer (A.A.-R.).

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Correspondence to Annemieke Aartsma-Rus.

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Competing interests

D.D. is a member of the scientific advisory board for Solid Biosciences and an equity holder of Solid Biosciences. D.D. is an inventor on patents licensed to various companies. D.D. has served as an ad hoc consultant for 4DMT, Decibel Therapeutics, Evox, Primary Insight, Vida Ventures, Global Guidepoint and GLG consultancy in the past 3 years. The lab of D.D. has received research support from Solid Biosciences and Edgewise Therapeutics in the past 3 years. N.G. has received compensation as member of scientific boards or as speaker at symposia from Sarepta, Pfizer, Italpharmaco and PTC Therapeutics. S.T. has patents on sequences for exon skip by antisense nucleic acids as a member of NCNP together with Nippon Shinyaku. As principal inventor of these patents, S.T. is entitled to a share of royalties. S.T. discloses being an ad hoc consultant for Ono Pharmaceutical, Daiichisankyo, Asahikasei Pharma, Teijin Pharma, AGADA Biosciences, and Wave and being a member of the scientific advisory boards of Nippon Shinyaku, Taiho Pharma and Sarepta therapeutics. S.T. received speaker honoraria from Japan Health Science Foundation and Astellas Pharma and has also received research supports from Taiho Pharma, Daiichisankyo, Nippon Shinyaku, Takeda Pharmaceutical and the Noguchi Institute in the past 3 years. E.M. is a Principal Investigator in clinical trials and advisory board member for Sarepta, Santhera, PTC, Roche, Italfarmaco, NS Pharma and Pfizer. A.A.-R. discloses being employed by Leiden University Medical Center (LUMC), which has patents on exon-skipping technology, some of which has been licensed to BioMarin and subsequently sublicensed to Sarepta. As co-inventor of some of these patents, A.A.-R. is entitled to a share of royalties. A.A.-R. further discloses being an ad hoc consultant for PTC Therapeutics, Sarepta Therapeutics, CRISPR Therapeutics, Summit PLC, Alpha Anomeric, BioMarin Pharmaceuticals Inc., Eisai, Astra Zeneca, Santhera, Audentes, Global Guidepoint and GLG consultancy, Grunenthal, Wave, and BioClinica, having been a member of the Duchenne Network Steering Committee (BioMarin), and being a member of the scientific advisory boards of ProQR, Hybridize Therapeutics, Silence Therapeutics, Sarepta Therapeutics and Philae Pharmaceuticals. Remuneration for these activities is paid to LUMC. LUMC also received speaker honoraria from PTC Therapeutics and BioMarin Pharmaceuticals and funding for contract research from Italpharmaco and Alpha Anomeric. Project funding is received from Sarepta Therapeutics.

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Nature Reviews Disease Primers thanks J. Novak, who co-reviewed with T. Partridge, P. Clemens, H. Gordish-Dressman, M. Ryan, J. Tremblay, and the other, anonymous, reviewer(s) for their contribution to the peer review of this work.

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Duan, D., Goemans, N., Takeda, S. et al. Duchenne muscular dystrophy. Nat Rev Dis Primers 7, 13 (2021). https://doi.org/10.1038/s41572-021-00248-3

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