{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,30]],"date-time":"2026-10-30T07:50:06Z","timestamp":1793346606810,"version":"4.5.0"},"reference-count":32,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2024,10,8]],"date-time":"2024-10-08T00:00:00Z","timestamp":1728345600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2024,10,8]],"date-time":"2024-10-08T00:00:00Z","timestamp":1728345600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>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). Male participants aged\u2009\u2265\u20098\u00a0years with DMD received 80\u00a0mg\/kg intravenous viltolarsen once weekly for 48\u00a0weeks. Results from participants receiving viltolarsen were compared with an external control cohort group-matched for multiple variables. All treatment-emergent adverse events were mild or moderate, 4 were considered treatment-related, and no participants discontinued. Participants receiving viltolarsen experienced clinically meaningful benefits in pulmonary function with higher percent predicted forced vital capacity and higher peak cough flow at Week 49 compared with the control cohort for both ambulatory and nonambulatory participants. Viltolarsen also stabilized upper limb motor function over the Treatment Period. These results support viltolarsen as an important part of the treatment armamentarium for both ambulatory as well as nonambulatory patients with DMD.<\/jats:p>","DOI":"10.1038\/s41598-024-70783-y","type":"journal-article","created":{"date-parts":[[2024,10,8]],"date-time":"2024-10-08T17:02:06Z","timestamp":1728406926000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Safety and efficacy of viltolarsen in ambulatory and nonambulatory males with Duchenne muscular dystrophy"],"prefix":"10.1038","volume":"14","author":[{"given":"Amy D.","family":"Harper","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haluk","family":"Topaloglu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eugenio","family":"Mercuri","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vasiliy","family":"Suslov","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liwen","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cigdem Y.","family":"Ayanoglu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Tansey","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michelle L.","family":"Previtera","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert A.","family":"Crozier","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leslie","family":"Magnus","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paula R.","family":"Clemens","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,10,8]]},"reference":[{"key":"70783_CR1","doi-asserted-by":"publisher","first-page":"482","DOI":"10.1016\/j.nmd.2014.03.008","volume":"24","author":"JK Mah","year":"2014","unstructured":"Mah, J. K. et al. A systematic review and meta-analysis on the epidemiology of Duchenne and Becker muscular dystrophy. Neuromuscul. Disord. 24, 482\u2013491. https:\/\/doi.org\/10.1016\/j.nmd.2014.03.008 (2014).","journal-title":"Neuromuscul. Disord."},{"key":"70783_CR2","doi-asserted-by":"publisher","first-page":"919","DOI":"10.1016\/0092-8674(87)90579-4","volume":"51","author":"EP Hoffman","year":"1987","unstructured":"Hoffman, E. P., Brown, R. H. Jr. & Kunkel, L. M. Dystrophin: The protein product of the Duchenne muscular dystrophy locus. Cell 51, 919\u2013928. https:\/\/doi.org\/10.1016\/0092-8674(87)90579-4 (1987).","journal-title":"Cell"},{"key":"70783_CR3","doi-asserted-by":"publisher","first-page":"395","DOI":"10.1002\/humu.22758","volume":"36","author":"CL Bladen","year":"2015","unstructured":"Bladen, C. L. et al. The TREAT-NMD DMD global database: Analysis of more than 7,000 Duchenne muscular dystrophy mutations. Hum. Mutat. 36, 395\u2013402. https:\/\/doi.org\/10.1002\/humu.22758 (2015).","journal-title":"Hum. Mutat."},{"key":"70783_CR4","doi-asserted-by":"publisher","first-page":"280","DOI":"10.1002\/ana.25951","volume":"89","author":"Y de Feraudy","year":"2021","unstructured":"de Feraudy, Y. et al. Very low residual dystrophin quantity is associated with milder dystrophinopathy. Ann. Neurol. 89, 280\u2013292. https:\/\/doi.org\/10.1002\/ana.25951 (2021).","journal-title":"Ann. Neurol."},{"key":"70783_CR5","doi-asserted-by":"publisher","first-page":"77","DOI":"10.1016\/S1474-4422(09)70271-6","volume":"9","author":"K Bushby","year":"2010","unstructured":"Bushby, K. et al. Diagnosis and management of Duchenne muscular dystrophy, part 1: Diagnosis, and pharmacological and psychosocial management. Lancet Neurol. 9, 77\u201393. https:\/\/doi.org\/10.1016\/S1474-4422(09)70271-6 (2010).","journal-title":"Lancet Neurol."},{"key":"70783_CR6","doi-asserted-by":"publisher","first-page":"347","DOI":"10.1016\/S1474-4422(18)30025-5","volume":"17","author":"DJ Birnkrant","year":"2018","unstructured":"Birnkrant, D. J. et al. Diagnosis and management of Duchenne muscular dystrophy, part 2: Respiratory, cardiac, bone health, and orthopaedic management. Lancet Neurol. 17, 347\u2013361. https:\/\/doi.org\/10.1016\/S1474-4422(18)30025-5 (2018).","journal-title":"Lancet Neurol."},{"key":"70783_CR7","doi-asserted-by":"publisher","first-page":"e1540","DOI":"10.1212\/WNL.0000000000201626","volume":"100","author":"F Muntoni","year":"2023","unstructured":"Muntoni, F. et al. DMD genotypes and motor function in Duchenne muscular dystrophy: A multi-institution meta-analysis with implications for clinical trials. Neurology 100, e1540\u2013e1554. https:\/\/doi.org\/10.1212\/WNL.0000000000201626 (2023).","journal-title":"Neurology"},{"key":"70783_CR8","first-page":"117","volume":"31","author":"S Rall","year":"2012","unstructured":"Rall, S. & Grimm, T. Survival in Duchenne muscular dystrophy. Acta Myol. 31, 117\u2013120 (2012).","journal-title":"Acta Myol."},{"key":"70783_CR9","doi-asserted-by":"publisher","first-page":"373","DOI":"10.1038\/s41582-019-0203-3","volume":"15","author":"IEC Verhaart","year":"2019","unstructured":"Verhaart, I. E. C. & Aartsma-Rus, A. Therapeutic developments for Duchenne muscular dystrophy. Nat. Rev. Neurol. 15, 373\u2013386. https:\/\/doi.org\/10.1038\/s41582-019-0203-3 (2019).","journal-title":"Nat. Rev. Neurol."},{"key":"70783_CR10","doi-asserted-by":"publisher","first-page":"32","DOI":"10.1002\/mus.23807","volume":"48","author":"CM McDonald","year":"2013","unstructured":"McDonald, C. M. et al. The cooperative international neuromuscular research group Duchenne natural history study\u2014A longitudinal investigation in the era of glucocorticoid therapy: Design of protocol and the methods used. Muscle Nerve 48, 32\u201354. https:\/\/doi.org\/10.1002\/mus.23807 (2013).","journal-title":"Muscle Nerve"},{"key":"70783_CR11","doi-asserted-by":"publisher","first-page":"1275","DOI":"10.1177\/0883073814558120","volume":"30","author":"S Kim","year":"2015","unstructured":"Kim, S. et al. Corticosteroid treatments in males with Duchenne muscular dystrophy: Treatment duration and time to loss of ambulation. J. Child Neurol. 30, 1275\u20131280. https:\/\/doi.org\/10.1177\/0883073814558120 (2015).","journal-title":"J. Child Neurol."},{"key":"70783_CR12","doi-asserted-by":"publisher","first-page":"90","DOI":"10.33590\/emj\/10311993","volume":"2","author":"H Van Ruiten","year":"2017","unstructured":"Van Ruiten, H., Bushby, K. & Guglieri, M. State-of-the-art advances in Duchenne muscular dystrophy. Eur. Med. J. 2, 90\u201399. https:\/\/doi.org\/10.33590\/emj\/10311993 (2017).","journal-title":"Eur. Med. J."},{"key":"70783_CR13","doi-asserted-by":"publisher","first-page":"291","DOI":"10.1152\/physrev.00028.2001","volume":"82","author":"DJ Blake","year":"2002","unstructured":"Blake, D. J., Weir, A., Newey, S. E. & Davies, K. E. Function and genetics of dystrophin and dystrophin-related proteins in muscle. Physiol. Rev. 82, 291\u2013329. https:\/\/doi.org\/10.1152\/physrev.00028.2001 (2002).","journal-title":"Physiol. Rev."},{"key":"70783_CR14","doi-asserted-by":"publisher","first-page":"1241","DOI":"10.3390\/genes13071241","volume":"13","author":"G Eser","year":"2022","unstructured":"Eser, G. & Topaloglu, H. Current outline of exon skipping trials in Duchenne muscular dystrophy. Genes 13, 1241. https:\/\/doi.org\/10.3390\/genes13071241 (2022).","journal-title":"Genes"},{"key":"70783_CR15","doi-asserted-by":"publisher","first-page":"2025","DOI":"10.1016\/S0140-6736(19)32910-1","volume":"394","author":"E Mercuri","year":"2019","unstructured":"Mercuri, E., Bonnemann, C. G. & Muntoni, F. Muscular dystrophies. Lancet 394, 2025\u20132038. https:\/\/doi.org\/10.1016\/S0140-6736(19)32910-1 (2019).","journal-title":"Lancet"},{"key":"70783_CR16","volume-title":"Prescribing Information","author":"VILTEPSO","year":"2021","unstructured":"VILTEPSO. Prescribing Information (NS Pharma Inc., 2021)."},{"key":"70783_CR17","unstructured":"NS Pharma Reports on Results of VILTEPSO\u00ae (viltolarsen) Injection After Four Years of Treatment in Open-Label Extension Trial in Duchenne Muscular Dystrophy. https:\/\/www.nspharma.com\/pdfs\/WMS_Data_Press_Release_final.pdf (Accessed 6 February 2024) (2022)."},{"key":"70783_CR18","doi-asserted-by":"publisher","first-page":"442","DOI":"10.1016\/j.omtn.2018.09.017","volume":"13","author":"N Watanabe","year":"2018","unstructured":"Watanabe, N. et al. NS-065\/NCNP-01: An antisense oligonucleotide for potential treatment of exon 53 skipping in Duchenne muscular dystrophy. Mol. Ther. Nucleic Acids 13, 442\u2013449. https:\/\/doi.org\/10.1016\/j.omtn.2018.09.017 (2018).","journal-title":"Mol. Ther. Nucleic Acids"},{"key":"70783_CR19","doi-asserted-by":"publisher","first-page":"439","DOI":"10.3233\/JND-221656","volume":"10","author":"PR Clemens","year":"2023","unstructured":"Clemens, P. R. et al. Efficacy and safety of viltolarsen in boys with Duchenne muscular dystrophy: Results from the phase 2, open-label, 4-year extension study. J. Neuromuscul. Dis. 10, 439\u2013447. https:\/\/doi.org\/10.3233\/JND-221656 (2023).","journal-title":"J. Neuromuscul. Dis."},{"key":"70783_CR20","doi-asserted-by":"publisher","first-page":"982","DOI":"10.1001\/jamaneurol.2020.1264","volume":"77","author":"PR Clemens","year":"2020","unstructured":"Clemens, P. R. et al. Safety, tolerability, and efficacy of viltolarsen in boys with Duchenne muscular dystrophy amenable to exon 53 skipping: A phase 2 randomized clinical trial. JAMA Neurol. 77, 982\u2013991. https:\/\/doi.org\/10.1001\/jamaneurol.2020.1264 (2020).","journal-title":"JAMA Neurol."},{"key":"70783_CR21","doi-asserted-by":"publisher","first-page":"2393","DOI":"10.1002\/acn3.51235","volume":"7","author":"H Komaki","year":"2020","unstructured":"Komaki, H. et al. Viltolarsen in Japanese Duchenne muscular dystrophy patients: A phase 1\/2 study. Ann. Clin. Transl. Neurol. 7, 2393\u20132408. https:\/\/doi.org\/10.1002\/acn3.51235 (2020).","journal-title":"Ann. Clin. Transl. Neurol."},{"key":"70783_CR22","doi-asserted-by":"publisher","first-page":"456","DOI":"10.1164\/rccm.200307-885ST","volume":"170","author":"JD Finder","year":"2004","unstructured":"Finder, J. D. et al. Respiratory care of the patient with Duchenne muscular dystrophy: ATS consensus statement. Am. J. Respir. Crit. Care Med. 170, 456\u2013465. https:\/\/doi.org\/10.1164\/rccm.200307-885ST (2004).","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"70783_CR23","doi-asserted-by":"publisher","first-page":"13","DOI":"10.1016\/j.prrv.2018.08.003","volume":"30","author":"OH Mayer","year":"2019","unstructured":"Mayer, O. H. Pulmonary function and clinical correlation in DMD. Paediatr. Respir. 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Lancet Neurol. 17, 445\u2013455. https:\/\/doi.org\/10.1016\/S1474-4422(18)30026-7 (2018).","journal-title":"Lancet Neurol."},{"key":"70783_CR30","first-page":"1107","volume":"69","author":"TJ Barreiro","year":"2004","unstructured":"Barreiro, T. J. & Perillo, I. An approach to interpreting spirometry. Am. Fam. Phys. 69, 1107\u20131114 (2004).","journal-title":"Am. Fam. Phys."},{"key":"70783_CR31","doi-asserted-by":"publisher","first-page":"567","DOI":"10.3233\/JND-221556","volume":"10","author":"M Pane","year":"2023","unstructured":"Pane, M. et al. Longitudinal analysis of PUL 2.0 domains in ambulant and non-ambulant Duchenne muscular dystrophy patients: How do they change in relation to functional ability? J. Neuromuscul. Dis. 10, 567\u2013574. https:\/\/doi.org\/10.3233\/JND-221556 (2023).","journal-title":"J. Neuromuscul. 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PLoS ONE 11, e0160195. https:\/\/doi.org\/10.1371\/journal.pone.0160195 (2016).","journal-title":"PLoS ONE"}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-024-70783-y.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-024-70783-y","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-024-70783-y.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,10,8]],"date-time":"2024-10-08T17:05:39Z","timestamp":1728407139000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-024-70783-y"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,10,8]]},"references-count":32,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2024,12]]}},"alternative-id":["70783"],"URL":"https:\/\/doi.org\/10.1038\/s41598-024-70783-y","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,10,8]]},"assertion":[{"value":"16 April 2024","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"21 August 2024","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"8 October 2024","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"ADH is a site principal investigator for clinical research studies sponsored by Astellas, Dyne, Fulcrum, Italafarmaco, MLBio, Novartis, Reveregan\/Santhera, and NS Pharma, Inc.; HT reports no conflicts of interest; EM is a principal investigator and consultant (advisory board) for Italfarmaco, Pfizer, PTC, Roche, Santhera, Sarepta, and NS Pharma, Inc.; VS reports no conflicts of interest; LW reports no conflicts of interest; CYA reports no conflicts of interest; MT reports employment for NS Pharma, Inc.; MLP reports employment for NS Pharma, Inc.; RAC reports employment for NS Pharma, Inc.; LM reports employment for NS Pharma, Inc.; PRC reports grants from Amicus, the US Food and Drug Administration, Foundation to Eradicate Duchenne, Hoffman-La Roche, the National Institutes of Health, Sanofi, Spark, and NS Pharma, Inc. and consulting\/advisory roles for Catalyst Education and Med Learning Group.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"23488"}}