{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T18:35:40Z","timestamp":1790534140497,"version":"4.1.0"},"reference-count":18,"publisher":"SAGE Publications","issue":"4","license":[{"start":{"date-parts":[[2022,7,1]],"date-time":"2022-07-01T00:00:00Z","timestamp":1656633600000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JND"],"published-print":{"date-parts":[[2022,7,1]]},"abstract":"<jats:p>Background: Duchenne muscular dystrophy (DMD) is a rare, genetic disease caused by mutations in the DMD gene resulting in an absence of functional dystrophin protein. Viltolarsen, an exon 53 skipping therapy, has been shown to increase endogenous dystrophin levels. Herein, long-term (&gt;2 years) functional outcomes in viltolarsen treated patients were compared to a matched historical control group. Objective: To evaluate long-term efficacy and safety of the anti-sense oligonucleotide viltolarsen in the treatment of patients with DMD amenable to exon 53 skipping therapy. Methods: This trial (NCT03167255) is the extension of a previously published 24-week trial in North America (NCT02740972) that examined dystrophin levels, timed function tests compared to a matched historical control group (Cooperative International Neuromuscular Research Group Duchenne Natural History Study, CINRG DNHS), and safety in boys 4 to\u200a&lt;\u200a10 years (N\u200a=\u200a16) with DMD amenable to exon 53 skipping who were treated with viltolarsen. Both groups were treated with glucocorticoids. All 16 participants elected to enroll in this long-term trial (up to 192 weeks) to continue evaluation of motor function and safety. Results: Time to stand from supine and time to run\/walk 10 meters showed stabilization from baseline through week 109 for viltolarsen-treated participants whereas the historical control group showed decline (statistically significant differences for multiple timepoints). Safety was similar to that observed in the previous 24-week trial, which was predominantly mild. There have been no treatment-related serious adverse events and no discontinuations. Conclusions: Based on these results at over 2 years, viltolarsen can be a new treatment option for patients with DMD amenable to exon 53 skipping.<\/jats:p>","DOI":"10.3233\/jnd-220811","type":"journal-article","created":{"date-parts":[[2022,5,24]],"date-time":"2022-05-24T11:54:43Z","timestamp":1653393283000},"page":"493-501","source":"Crossref","is-referenced-by-count":62,"title":["Long-Term Functional Efficacy and Safety of Viltolarsen in Patients with Duchenne Muscular Dystrophy"],"prefix":"10.1177","volume":"9","author":[{"given":"Paula R.","family":"Clemens","sequence":"first","affiliation":[{"name":"Department of Neurology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania"},{"name":"Department of Veterans Affairs Medical Center, Pittsburgh, Pennsylvania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"the CINRG DNHS Investigators","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vamshi K.","family":"Rao","sequence":"additional","affiliation":[{"name":"Division of Neurology, Ann and Robert H. Lurie Children\u2019s Hospital of Chicago, Chicago, Illinois"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne M.","family":"Connolly","sequence":"additional","affiliation":[{"name":"Division of Neurology, Nationwide Children\u2019s Hospital, The Ohio State University College of Medicine, Columbus, Ohio"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amy D.","family":"Harper","sequence":"additional","affiliation":[{"name":"Children\u2019s Hospital of Richmond at Virginia Commonwealth University, Richmond, Virginia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean K.","family":"Mah","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of Calgary, Calgary, Alberta, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Craig M.","family":"McDonald","sequence":"additional","affiliation":[{"name":"Department of Physical Medicine and Rehabilitation, Department of Pediatrics, UC Davis Health, University of California, Davis, Sacramento, California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edward C.","family":"Smith","sequence":"additional","affiliation":[{"name":"Duke University Medical Center, Durham, North Carolina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Craig M.","family":"Zaidman","sequence":"additional","affiliation":[{"name":"Department of Neurology, Washington University at St Louis, St Louis, Missouri"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomoyuki","family":"Nakagawa","sequence":"additional","affiliation":[{"name":"NS Pharma, Inc, Paramus, New Jersey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric P.","family":"Hoffman","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, State University of New York at Binghamton, Binghamton, New York"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","reference":[{"issue":"6","key":"10.3233\/JND-220811_ref1","doi-asserted-by":"crossref","first-page":"482","DOI":"10.1016\/j.nmd.2014.03.008","article-title":"A systematic review and meta-analysis on the epidemiology of Duchenne and Becker muscular dystrophy","volume":"24","author":"Mah","year":"2014","journal-title":"Neuromuscul Disord"},{"issue":"6","key":"10.3233\/JND-220811_ref2","doi-asserted-by":"crossref","first-page":"919","DOI":"10.1016\/0092-8674(87)90579-4","article-title":"Dystrophin: the protein product of the Duchenne muscular dystrophy locus","volume":"51","author":"Hoffman","year":"1987","journal-title":"Cell"},{"issue":"4","key":"10.3233\/JND-220811_ref3","doi-asserted-by":"crossref","first-page":"395","DOI":"10.1002\/humu.22758","article-title":"The TREAT-NMD DMD Global Database: analysis of more than 7,000 Duchenne muscular dystrophy mutations","volume":"36","author":"Bladen","year":"2015","journal-title":"Hum Mutat"},{"issue":"1","key":"10.3233\/JND-220811_ref4","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1016\/S1474-4422(09)70271-6","article-title":"Diagnosis and management of Duchenne muscular dystrophy, part diagnosis, and pharmacological and psychosocial management","volume":"9","author":"Bushby","year":"2010","journal-title":"Lancet Neurol."},{"issue":"2","key":"10.3233\/JND-220811_ref5","doi-asserted-by":"crossref","first-page":"280","DOI":"10.1002\/ana.25951","article-title":"Very low residual dystrophin quantity Is associated with milder dystrophinopathy","volume":"89","author":"de Feraudy","year":"2021","journal-title":"Ann Neurol"},{"issue":"1","key":"10.3233\/JND-220811_ref6","doi-asserted-by":"crossref","first-page":"176","DOI":"10.1002\/ana.26097","article-title":"Concerns regarding therapeutic implications of very low-level dystrophin","volume":"90","author":"Hoffman","year":"2021","journal-title":"Ann Neurol"},{"issue":"1","key":"10.3233\/JND-220811_ref7","first-page":"54","article-title":"Exploring the molecular basis for variability among patients with Becker muscular dystrophy: dystrophin gene and protein studies","volume":"49","author":"Beggs","year":"1991","journal-title":"Am J Hum Genet"},{"issue":"7","key":"10.3233\/JND-220811_ref8","doi-asserted-by":"crossref","first-page":"373","DOI":"10.1038\/s41582-019-0203-3","article-title":"Therapeutic developments for Duchenne muscular dystrophy","volume":"15","author":"Verhaart","year":"2019","journal-title":"Nat Rev Neurol"},{"key":"10.3233\/JND-220811_ref9","doi-asserted-by":"crossref","unstructured":"Komaki H , Nagata T , Saito T , Masuda S , Takeshita E , Sasaki M , et al., Systemic administration of the antisense oligonucleotide NS-065\/NCNP-01 for skipping of exon 53 in patients with Duchenne muscular dystrophy. Sci Transl Med 2018;10(437).","DOI":"10.1126\/scitranslmed.aan0713"},{"key":"10.3233\/JND-220811_ref11","doi-asserted-by":"crossref","first-page":"442","DOI":"10.1016\/j.omtn.2018.09.017","article-title":"NS-065\/NCNP- an antisense oligonucleotide for potential treatment of exon 53 skipping in Duchenne muscular dystrophy","volume":"13","author":"Watanabe","year":"2018","journal-title":"Mol Ther Nucleic Acids"},{"issue":"12","key":"10.3233\/JND-220811_ref12","doi-asserted-by":"crossref","first-page":"2393","DOI":"10.1002\/acn3.51235","article-title":"Viltolarsen in Japanese Duchenne muscular dystrophy patients: A phase 1\/2 study","volume":"7","author":"Komaki","year":"2020","journal-title":"Ann Clin Transl Neurol"},{"issue":"8","key":"10.3233\/JND-220811_ref13","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"},{"issue":"9","key":"10.3233\/JND-220811_ref20","doi-asserted-by":"crossref","first-page":"1217","DOI":"10.4155\/cli.11.113","article-title":"Clinical outcome measures for trials in Duchenne muscular dystrophy: report from International Working Group meetings","volume":"1","author":"Bushby","year":"2011","journal-title":"Clin Investig (Lond)"},{"issue":"1","key":"10.3233\/JND-220811_ref21","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1089\/nat.2021.0043","article-title":"SKIP-NMD Study GrouLong-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"},{"issue":"2","key":"10.3233\/JND-220811_ref22","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1002\/ana.24555","article-title":"Eteplirsen Study Group and Telethon Foundation DMD Italian Network Longitudinal effect of eteplirsen versus historical control on ambulation in Duchenne muscular dystrophy","volume":"79","author":"Mendell","year":"2016","journal-title":"Ann Neurol"},{"issue":"1","key":"10.3233\/JND-220811_ref23","doi-asserted-by":"crossref","first-page":"47","DOI":"10.3233\/JND-170272","article-title":"Long-term pulmonary function in Duchenne muscular dystrophy: comparison of eteplirsen-treated patients to natural history","volume":"5","author":"Kinane","year":"2018","journal-title":"J Neuromuscul Dis"},{"issue":"4","key":"10.3233\/JND-220811_ref24","doi-asserted-by":"crossref","first-page":"469","DOI":"10.3233\/JND-200548","article-title":"Comparison of long-term ambulatory function in patients with Duchenne muscular dystrophy treated with eteplirsen and matched natural history controls","volume":"8","author":"Mendell","year":"2021","journal-title":"J Neuromuscul Dis"},{"issue":"10","key":"10.3233\/JND-220811_ref25","doi-asserted-by":"crossref","first-page":"e1381","DOI":"10.1212\/WNL.0000000000010170","article-title":"Suitability of external controls for drug evaluation in Duchenne muscular dystrophy","volume":"95","author":"Goemans","year":"2020","journal-title":"Neurology"}],"container-title":["Journal of Neuromuscular Diseases"],"original-title":[],"link":[{"URL":"https:\/\/content.iospress.com\/download?id=10.3233\/JND-220811","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T23:50:00Z","timestamp":1777506600000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.sagepub.com\/doi\/full\/10.3233\/JND-220811"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,7,1]]},"references-count":18,"journal-issue":{"issue":"4"},"URL":"https:\/\/doi.org\/10.3233\/jnd-220811","relation":{},"ISSN":["2214-3599","2214-3602"],"issn-type":[{"value":"2214-3599","type":"print"},{"value":"2214-3602","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,7,1]]}}}