{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T05:45:27Z","timestamp":1789623927810,"version":"build-2803163510"},"reference-count":45,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2026,3,12]],"date-time":"2026-03-12T00:00:00Z","timestamp":1773273600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Muscles"],"abstract":"<jats:p>Duchenne muscular dystrophy (DMD) is a severe X-linked neuromuscular disorder caused by loss-of-function mutations in the dystrophin gene, leading to progressive muscle degeneration, motor decline, respiratory compromise, and cardiomyopathy. Diagnosis typically occurs in early childhood following recognition of motor delays, markedly elevated creatine kinase, and confirmatory genetic testing. Over the past decade, the therapeutic landscape for DMD has expanded substantially, evolving from exclusively supportive care to patient-centric multifaceted treatment paradigms, including corticosteroids, mutation-specific therapies, small molecule disease-modifying approaches, and gene replacement strategies. Despite these advances, no currently available therapy restores full-length dystrophin or completely halts disease progression. This review provides a clinically oriented comprehensive overview of currently Food and Drug Administration (FDA)-approved medications for DMD, with particular emphasis on corticosteroids, exon-skipping therapies, nonsense mutation readthrough agents, recently approved gene therapy, and select ongoing gene therapy trials. We summarize mechanisms of action, clinical efficacy, safety considerations, regulatory status, and highlight the challenges of integrating these therapies into longitudinal care. Through illustrative clinical vignettes, we highlight the real-world complexity of treatment selection, shared decision-making, and longitudinal care planning in contemporary DMD management.<\/jats:p>","DOI":"10.3390\/muscles5010021","type":"journal-article","created":{"date-parts":[[2026,3,12]],"date-time":"2026-03-12T09:23:03Z","timestamp":1773307383000},"page":"21","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Duchenne Muscular Dystrophy: Contemporary Therapeutic Options and Real-World Challenges in Treatment Selection"],"prefix":"10.3390","volume":"5","author":[{"given":"Maria Tozzo","family":"Pesco","sequence":"first","affiliation":[{"name":"Department of Genetic and Cellular Medicine, UMass Chan Medical School, Worcester, MA 01655, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-4955-5748","authenticated-orcid":false,"given":"G\u00fclru Zeynep","family":"\u00d6zt\u00fcrk","sequence":"additional","affiliation":[{"name":"School of Medicine, Ankara University, Ankara 06230, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9112-5658","authenticated-orcid":false,"given":"Shivkumar C.","family":"Bhadola","sequence":"additional","affiliation":[{"name":"Department of Neurology, UMass Chan Medical School, Worcester, MA 01655, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4321-5661","authenticated-orcid":false,"given":"Stephen M.","family":"Chrzanowski","sequence":"additional","affiliation":[{"name":"Department of Neurology, UMass Chan Medical School, Worcester, MA 01655, USA"},{"name":"Department of Pediatrics, UMass Chan Medical School, Worcester, MA 01655, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5639-442X","authenticated-orcid":false,"given":"Liubov V.","family":"Gushchina","sequence":"additional","affiliation":[{"name":"The Jerry R. Mendell Center for Gene Therapy, Nationwide Children\u2019s Hospital, Columbus, OH 43215, USA"},{"name":"Department of Pediatrics, The Ohio State University, Columbus, OH 43205, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eleonora S.","family":"D\u2019Ambrosio","sequence":"additional","affiliation":[{"name":"Department of Genetic and Cellular Medicine, UMass Chan Medical School, Worcester, MA 01655, USA"},{"name":"Department of Neurology, UMass Chan Medical School, Worcester, MA 01655, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,3,12]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2529","DOI":"10.1097\/MS9.0000000000003196","article-title":"Duvyzat (givinostat): A new hope for Duchenne muscular dystrophy patients","volume":"87","author":"Syed","year":"2025","journal-title":"Ann. Med. Surg."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Kemper, A.R., Lam, W.K., Ojodu, J., Jones, E., Smith, H.S., Comeau, A.M., Tanksley, S., Ream, M.A., and Grosse, S.D. (2025). Evidence Regarding Duchenne Muscular Dystrophy Newborn Screening. Pediatrics, in press.","DOI":"10.1542\/peds.2025-073192"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1016\/S1474-4422(18)30024-3","article-title":"Diagnosis and management of Duchenne muscular dystrophy, part 1: Diagnosis, and neuromuscular, rehabilitation, endocrine, and gastrointestinal and nutritional management","volume":"17","author":"Birnkrant","year":"2018","journal-title":"Lancet Neurol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1038\/s41572-021-00248-3","article-title":"Duchenne muscular dystrophy","volume":"7","author":"Duan","year":"2021","journal-title":"Nat. Rev. Dis. Primers"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1136\/jmedgenet-2015-103387","article-title":"The importance of genetic diagnosis for Duchenne muscular dystrophy","volume":"53","author":"Ginjaar","year":"2016","journal-title":"J. Med. Genet."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"443","DOI":"10.1016\/j.rehab.2013.06.002","article-title":"Evolution of life expectancy of patients with Duchenne muscular dystrophy at AFM Yolaine de Kepper centre between 1981 and 2011","volume":"56","author":"Kieny","year":"2013","journal-title":"Ann. Phys. Rehabil. Med."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1007\/s40265-023-01986-2","article-title":"Vamorolone: First Approval","volume":"84","author":"Keam","year":"2024","journal-title":"Drugs"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"444","DOI":"10.1212\/WNL.0b013e318227b164","article-title":"Randomized, blinded trial of weekend vs daily prednisone in Duchenne muscular dystrophy","volume":"77","author":"Escolar","year":"2011","journal-title":"Neurology"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"695","DOI":"10.1007\/s40272-024-00655-5","article-title":"Efficacy and Safety of Vamorolone in Duchenne Muscular Dystrophy: A Systematic Review","volume":"26","year":"2024","journal-title":"Paediatr. Drugs"},{"key":"ref_10","first-page":"ecurrents-md","article-title":"The PJ Nicholoff Steroid Protocol for Duchenne and Becker Muscular Dystrophy and Adrenal Suppression","volume":"9","author":"Kinnett","year":"2017","journal-title":"PLoS Curr."},{"key":"ref_11","unstructured":"ITF Therapeutics, LLC (2026, January 30). DUVYZAT\u2122 (Givinostat) for HCPs. Available online: https:\/\/www.duvyzathcp.com\/."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"849","DOI":"10.1007\/s40265-024-02052-1","article-title":"Givinostat: First Approval","volume":"84","author":"Lamb","year":"2024","journal-title":"Drugs"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"533","DOI":"10.2147\/DDDT.S97635","article-title":"Eteplirsen in the treatment of Duchenne muscular dystrophy","volume":"11","author":"Lim","year":"2017","journal-title":"Drug Des. Dev. Ther."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"372","DOI":"10.1089\/hum.2023.026","article-title":"The Future of Exon Skipping for Duchenne Muscular Dystrophy","volume":"34","year":"2023","journal-title":"Hum. Gene Ther."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"2025","DOI":"10.1016\/S0140-6736(19)32910-1","article-title":"Muscular dystrophies","volume":"394","author":"Mercuri","year":"2019","journal-title":"Lancet"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"637","DOI":"10.1002\/ana.23982","article-title":"Eteplirsen for the treatment of Duchenne muscular dystrophy","volume":"74","author":"Mendell","year":"2013","journal-title":"Ann. Neurol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1089\/nat.2021.0043","article-title":"Long-Term Safety and Efficacy Data of Golodirsen in Ambulatory Patients with Duchenne Muscular Dystrophy Amenable to Exon 53 Skipping: A First-in-human, Multicenter, Two-Part, Open-Label, Phase 1\/2 Trial","volume":"32","author":"Servais","year":"2022","journal-title":"Nucleic Acid. Ther."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"982","DOI":"10.1001\/jamaneurol.2020.1264","article-title":"Safety, Tolerability, and Efficacy of Viltolarsen in Boys with Duchenne Muscular Dystrophy Amenable to Exon 53 Skipping: A Phase 2 Randomized Clinical Trial","volume":"77","author":"Clemens","year":"2020","journal-title":"JAMA Neurol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"11401","DOI":"10.1093\/nar\/gkac641","article-title":"Enhanced exon skipping and prolonged dystrophin restoration achieved by TfR1-targeted delivery of antisense oligonucleotide using FORCE conjugation in mdx mice","volume":"50","author":"Desjardins","year":"2022","journal-title":"Nucleic Acids Res."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"e153837","DOI":"10.1172\/JCI153837","article-title":"Modulating fast skeletal muscle contraction protects skeletal muscle in animal models of Duchenne muscular dystrophy","volume":"133","author":"Russell","year":"2023","journal-title":"J. Clin. Investig."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"399","DOI":"10.1002\/mus.28444","article-title":"A Phase 1, Double-Blind, Placebo-Controlled Trial of Sevasemten (EDG-5506), a Selective Modulator of Fast Skeletal Muscle Contraction, in Healthy Volunteers and Adults with Becker Muscular Dystrophy","volume":"72","author":"Donovan","year":"2025","journal-title":"Muscle Nerve"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"10031","DOI":"10.1038\/s41467-025-64999-3","article-title":"Intrinsic dysfunction in muscle stem cells lacking dystrophin begins during secondary myogenesis","volume":"16","author":"Esper","year":"2025","journal-title":"Nat. Commun."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1038\/nature05756","article-title":"PTC124 targets genetic disorders caused by nonsense mutations","volume":"447","author":"Welch","year":"2007","journal-title":"Nature"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"477","DOI":"10.1002\/mus.24332","article-title":"Ataluren treatment of patients with nonsense mutation dystrophinopathy","volume":"50","author":"Bushby","year":"2014","journal-title":"Muscle Nerve"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1489","DOI":"10.1016\/S0140-6736(17)31611-2","article-title":"Ataluren in patients with nonsense mutation Duchenne muscular dystrophy (ACT DMD): A multicentre, randomised, double-blind, placebo-controlled, phase 3 trial","volume":"390","author":"McDonald","year":"2017","journal-title":"Lancet"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"3896","DOI":"10.1007\/s00415-023-11687-1","article-title":"Safety and effectiveness of ataluren in patients with nonsense mutation DMD in the STRIDE Registry compared with the CINRG Duchenne Natural History Study (2015\u20132022): 2022 interim analysis","volume":"270","author":"Mercuri","year":"2023","journal-title":"J. Neurol."},{"key":"ref_27","first-page":"37","article-title":"Clinical potential of ataluren in the treatment of Duchenne muscular dystrophy","volume":"6","author":"Namgoong","year":"2016","journal-title":"Degener. Neurol. Neuromuscul. Dis."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"973","DOI":"10.2217\/cer-2020-0095","article-title":"Meta-analyses of ataluren randomized controlled trials in nonsense mutation Duchenne muscular dystrophy","volume":"9","author":"Campbell","year":"2020","journal-title":"J. Comp. Eff. Res."},{"key":"ref_29","unstructured":"European Medicines Agency (2014). Translarna (Ataluren): European Public Assessment Report, European Medicines Agency."},{"key":"ref_30","unstructured":"US Food and Drug Administration (2014). Ataluren (PTC124) Summary Review and Advisory Committee Briefing Documents."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"180","DOI":"10.1038\/343180a0","article-title":"Very mild muscular dystrophy associated with the deletion of 46% of dystrophin","volume":"343","author":"England","year":"1990","journal-title":"Nature"},{"key":"ref_32","unstructured":"(2026, March 05). These Highlights Do not Include all the Information Needed to Use ELEVIDYS\u00ae Safely Effectively See Full Prescribing Information for ELEVIDYS. ELEVIDYS(delandistrogene moxeparvovec-rokl) Suspension for Intravenous Infusion. Initial U.S. Approval: 2023, Available online: https:\/\/www.fda.gov\/files\/vaccines%2C%20blood%20%26%20biologics\/published\/Package-Insert-ELEVIDYS_1.pdf."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"332","DOI":"10.1038\/s41591-024-03304-z","article-title":"AAV gene therapy for Duchenne muscular dystrophy: The EMBARK phase 3 randomized trial","volume":"31","author":"Mendell","year":"2025","journal-title":"Nat. Med."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"955","DOI":"10.1002\/ana.26755","article-title":"Delandistrogene Moxeparvovec Gene Therapy in Ambulatory Patients (Aged \u22654 to <8 Years) with Duchenne Muscular Dystrophy: 1-Year Interim Results from Study SRP-9001-103 (ENDEAVOR)","volume":"94","author":"Zaidman","year":"2023","journal-title":"Ann. Neurol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"e213604","DOI":"10.1212\/WNL.0000000000213604","article-title":"Delandistrogene Moxeparvovec Gene Therapy in Individuals With Duchenne Muscular Dystrophy: Evidence in Focus: Report of the AAN Guidelines Subcommittee","volume":"104","author":"Oskoui","year":"2025","journal-title":"Neurology"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1038\/s41598-024-84077-w","article-title":"Immunologic investigations into transgene directed immune-mediated myositis following delandistrogene moxeparvovec gene therapy","volume":"15","author":"Potter","year":"2025","journal-title":"Sci. Rep."},{"key":"ref_37","unstructured":"US Food and Drug Administration (2026, January 30). FDA Investigating Deaths due to Acute Liver Failure in Non-Ambulatory Duchenne Muscular Dystrophy Patients Following ELEVIDYS [Safety Communication], Available online: https:\/\/www.fda.gov\/vaccines-blood-biologics\/safety-availability-biologics\/fda-investigating-deaths-due-acute-liver-failure-non-ambulatory-duchenne-muscular-dystrophy-patients."},{"key":"ref_38","unstructured":"US Food and Drug Administration (2026, January 30). FDA Takes Action on New Boxed Warning for Acute Serious Liver Injury and Acute Liver Failure Following Treatment with Elevidys and Revised Indication that is Limited to Ambulatory Duchenne Muscular Dystrophy Patients [Safety Communication], Available online: https:\/\/www.fda.gov\/vaccines-blood-biologics\/safety-availability-biologics\/fda-takes-action-new-boxed-warning-acute-serious-liver-injury-and-acute-liver-failure-following."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"104424","DOI":"10.1016\/j.braindev.2025.104424","article-title":"Gene therapy for Duchenne muscular dystrophy","volume":"47","year":"2025","journal-title":"Brain Dev."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"101519","DOI":"10.1016\/j.omtm.2025.101519","article-title":"Enhanced therapeutic potential of a microdystrophin with an extended C-terminal domain","volume":"33","author":"Foltz","year":"2025","journal-title":"Mol. Ther. Methods Clin. Dev."},{"key":"ref_41","unstructured":"Solid Biosciences Inc (2018). Solid Biosciences Announces FDA Removes Clinical Hold on SGT-001 [Press Release], Solid Biosciences. Available online: https:\/\/investors.solidbio.com\/news-releases\/news-release-details\/solid-biosciences-announces-fda-removes-clinical-hold-sgt-001."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1429","DOI":"10.1056\/NEJMoa1000228","article-title":"Dystrophin immunity in Duchenne\u2019s muscular dystrophy","volume":"363","author":"Mendell","year":"2010","journal-title":"N. Engl. J. Med."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"447","DOI":"10.1038\/s41434-025-00561-6","article-title":"AAV microdystrophin gene replacement therapy for Duchenne muscular dystrophy: Progress and prospects","volume":"32","author":"Chwalenia","year":"2025","journal-title":"Gene Ther."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"393","DOI":"10.1016\/S1474-4422(24)00036-X","article-title":"Safety and efficacy of givinostat in boys with Duchenne muscular dystrophy (EPIDYS): A multicentre, randomised, double-blind, placebo-controlled, phase 3 trial","volume":"23","author":"Mercuri","year":"2024","journal-title":"Lancet Neurol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"814","DOI":"10.1016\/S1474-4422(22)00125-9","article-title":"Emerging therapies for Duchenne muscular dystrophy","volume":"21","author":"Markati","year":"2022","journal-title":"Lancet Neurol."}],"container-title":["Muscles"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2813-0413\/5\/1\/21\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,12]],"date-time":"2026-03-12T10:59:40Z","timestamp":1773313180000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2813-0413\/5\/1\/21"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,3,12]]},"references-count":45,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,3]]}},"alternative-id":["muscles5010021"],"URL":"https:\/\/doi.org\/10.3390\/muscles5010021","relation":{},"ISSN":["2813-0413"],"issn-type":[{"value":"2813-0413","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,3,12]]}}}