{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T11:24:22Z","timestamp":1790767462663,"version":"4.1.0"},"reference-count":32,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,7,11]],"date-time":"2023-07-11T00:00:00Z","timestamp":1689033600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell Dev. Biol."],"abstract":"<jats:p><jats:bold>Introduction:<\/jats:bold> Delandistrogene moxeparvovec (SRP-9001) is an investigational gene transfer therapy designed for targeted expression of SRP-9001 dystrophin protein, a shortened dystrophin retaining key functional domains of the wild-type protein.<\/jats:p><jats:p><jats:bold>Methods:<\/jats:bold> This Phase 2, double-blind, two-part (48\u00a0weeks per part) crossover study (SRP-9001-102 [Study 102]; NCT03769116) evaluated delandistrogene moxeparvovec in patients, aged \u22654 to &amp;lt;8\u00a0years with Duchenne muscular dystrophy. Primary endpoints (Part 1) were change from baseline (CFBL) in SRP-9001 dystrophin expression (Week 12), by Western blot, and in North Star Ambulatory Assessment (NSAA) score (Week 48). Safety assessments included treatment-related adverse events (TRAEs). Patients were randomized and stratified by age to placebo (n = 21) or delandistrogene moxeparvovec (n = 20) and crossed over for Part 2.<\/jats:p><jats:p><jats:bold>Results:<\/jats:bold> SRP-9001 dystrophin expression was achieved in all patients: mean CFBL to Week 12 was 23.82% and 39.64% normal in Parts 1 and 2, respectively. In Part 1, CFBL to Week 48 in NSAA score (least-squares mean, LSM [standard error]) was +1.7 (0.6) with treatment versus +0.9 (0.6) for placebo; <jats:italic>p<\/jats:italic> = 0.37. Disparity in baseline motor function between groups likely confounded these results. In 4- to 5-year-olds with matched baseline motor function, CFBL to Week 48 in NSAA scores was significantly different (+2.5 points; <jats:italic>p<\/jats:italic> = 0.0172), but not significantly different in 6-to-7-year-olds with imbalanced baseline motor function (\u22120.7 points; <jats:italic>p<\/jats:italic> = 0.5384). For patients treated with delandistrogene moxeparvovec in Part 2, CFBL to Week 48 in NSAA score was +1.3 (2.7), whereas for those treated in Part 1, NSAA scores were maintained. As all patients in Part 2 were exposed to treatment, results were compared with a propensity-score-weighted external control (EC) cohort. The LSM difference in NSAA score between the Part 2 treated group and EC cohort was statistically significant (+2.0 points; <jats:italic>p<\/jats:italic> = 0.0009). The most common TRAEs were vomiting, decreased appetite, and nausea. Most occurred within the first 90\u00a0days and all resolved.<\/jats:p><jats:p><jats:bold>Discussion:<\/jats:bold> Results indicate robust expression of SRP-9001 dystrophin and overall stabilization in NSAA up to 2\u00a0years post-treatment. Differences in NSAA between groups in Part 1 were not significant for the overall population, likely because cohorts were stratified only by age, and other critical prognostic factors were not well matched at baseline.<\/jats:p>","DOI":"10.3389\/fcell.2023.1167762","type":"journal-article","created":{"date-parts":[[2023,7,11]],"date-time":"2023-07-11T09:24:54Z","timestamp":1689067494000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":87,"title":["Expression of SRP-9001 dystrophin and stabilization of motor function up to 2 years post-treatment with delandistrogene moxeparvovec gene therapy in individuals with Duchenne muscular dystrophy"],"prefix":"10.3389","volume":"11","author":[{"given":"Jerry R.","family":"Mendell","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Perry B.","family":"Shieh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Craig M.","family":"McDonald","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zarife","family":"Sahenk","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kelly J.","family":"Lehman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Linda P.","family":"Lowes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natalie F.","family":"Reash","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Megan A.","family":"Iammarino","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lindsay N.","family":"Alfano","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brenna","family":"Sabo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeremy D.","family":"Woods","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christy L.","family":"Skura","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Howard C.","family":"Mao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Loretta A.","family":"Staudt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Danielle A.","family":"Griffin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah","family":"Lewis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shufang","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rachael A.","family":"Potter","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Teji","family":"Singh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Louise R.","family":"Rodino-Klapac","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2023,7,11]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","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":"B2","doi-asserted-by":"publisher","first-page":"2146","DOI":"10.1212\/WNL.0000000000005680","article-title":"Eteplirsen treatment for Duchenne muscular dystrophy: Exon skipping and dystrophin production","volume":"90","author":"Charleston","year":"2018","journal-title":"Neurology"},{"key":"B4","unstructured":"NCT01603407: Finding the optimum regimen for Duchenne muscular dystrophy (FOR-DMD)2012"},{"key":"B5","unstructured":"NCT01865084: A study of tadalafil for Duchenne muscular dystrophy2013"},{"key":"B3","unstructured":"NCT00468832: Longitudinal study of the natural history of Duchenne muscular dystrophy (DMD)2016"},{"key":"B6","unstructured":"NCT03769116: A randomized, double-blind, placebo-controlled study of SRP-9001 for Duchenne muscular dystrophy (DMD)2018"},{"key":"B7","unstructured":"NCT04626674: A gene delivery study to evaluate the safety of and expression from SRP-9001 in Duchenne muscular dystrophy (DMD) (ENDEAVOR)"},{"key":"B8","unstructured":"NCT05096221: A gene transfer therapy study to evaluate the safety and efficacy of SRP-9001 (delandistrogene moxeparvovec) in participants with Duchenne muscular dystrophy (DMD) (EMBARK)"},{"key":"B9","doi-asserted-by":"publisher","first-page":"84","DOI":"10.1186\/s12883-019-1304-8","article-title":"Variability and trends in corticosteroid use by male United States participants with Duchenne muscular dystrophy in the Duchenne Registry","volume":"19","author":"Cowen","year":"2019","journal-title":"BMC Neurol."},{"key":"B10","doi-asserted-by":"publisher","first-page":"S303","DOI":"10.3233\/JND-210678","article-title":"Gene therapy for Duchenne muscular dystrophy","volume":"8","author":"Elangkovan","year":"2021","journal-title":"J. Neuromuscul. Dis."},{"key":"B11","doi-asserted-by":"publisher","first-page":"465","DOI":"10.1212\/WNL.0000000000002337","article-title":"Practice guideline update summary: Corticosteroid treatment of Duchenne muscular dystrophy: Report of the Guideline Development Subcommittee of the American Academy of Neurology","volume":"86","author":"Gloss","year":"2016","journal-title":"Neurology"},{"key":"B12","doi-asserted-by":"publisher","first-page":"0161955","DOI":"10.1371\/journal.pone.0161955","article-title":"Long-term efficacy, safety, and pharmacokinetics of drisapersen in Duchenne muscular dystrophy: Results from an open-label extension study","volume":"11","author":"Goemans","year":"2016","journal-title":"PloS One"},{"key":"B13","doi-asserted-by":"publisher","first-page":"1381","DOI":"10.1212\/WNL.0000000000010170","article-title":"Suitability of external controls for drug evaluation in Duchenne muscular dystrophy","volume":"95","author":"Goemans","year":"","journal-title":"Neurology"},{"key":"B14","doi-asserted-by":"publisher","first-page":"0232870","DOI":"10.1371\/journal.pone.0232870","article-title":"Prognostic factors for changes in the timed 4-stair climb in patients with Duchenne muscular dystrophy, and implications for measuring drug efficacy: A multi-institutional collaboration","volume":"15","author":"Goemans","year":"","journal-title":"PLoS One"},{"key":"B15","first-page":"35","article-title":"Prenatal diagnosis of Duchenne muscular dystrophy by fetoscopic muscle biopsy. Report of a case","volume":"23","author":"Guo","year":"1990","journal-title":"Zhonghua Shen. Jing Jing Shen. Ke. Za. Zhi."},{"key":"B16","doi-asserted-by":"publisher","first-page":"8396429","DOI":"10.1155\/2020\/8396429","article-title":"Population-wide Duchenne muscular dystrophy carrier detection by CK and molecular testing","volume":"2020","author":"Han","year":"2020","journal-title":"Biomed. Res. Int."},{"key":"B17","doi-asserted-by":"publisher","first-page":"329","DOI":"10.1007\/s40265-020-01267-2","article-title":"Golodirsen: First approval","volume":"80","author":"Heo","year":"2020","journal-title":"Drugs"},{"key":"B18","doi-asserted-by":"publisher","first-page":"117","DOI":"10.1186\/s13023-021-01758-9","article-title":"Standard of care versus new-wave corticosteroids in the treatment of Duchenne muscular dystrophy: Can we do better?","volume":"16","author":"Kourakis","year":"2021","journal-title":"Orphanet J. Rare Dis."},{"key":"B19","doi-asserted-by":"publisher","first-page":"100877","DOI":"10.1016\/j.spen.2021.100877","article-title":"Therapeutic approaches for Duchenne muscular dystrophy: Old and new","volume":"37","author":"Mackenzie","year":"2021","journal-title":"Semin. Pediatr. Neurol."},{"key":"B20","doi-asserted-by":"publisher","first-page":"1429","DOI":"10.1056\/NEJMoa1000228","article-title":"Dystrophin immunity in Duchenne's muscular dystrophy","volume":"363","author":"Mendell","year":"2010","journal-title":"N. Engl. J. Med."},{"key":"B21","doi-asserted-by":"publisher","first-page":"1122","DOI":"10.1001\/jamaneurol.2020.1484","article-title":"Assessment of systemic delivery of rAAVrh74.MHCK7.micro-dystrophin in children with Duchenne muscular dystrophy: A nonrandomized controlled trial","volume":"77","author":"Mendell","year":"2020","journal-title":"JAMA Neurol."},{"key":"B22","doi-asserted-by":"publisher","first-page":"0221097","DOI":"10.1371\/journal.pone.0221097","article-title":"Categorising trajectories and individual item changes of the North Star Ambulatory Assessment in patients with Duchenne muscular dystrophy","volume":"14","author":"Muntoni","year":"2019","journal-title":"PLoS One"},{"key":"B23","doi-asserted-by":"publisher","first-page":"69","DOI":"10.1016\/j.nmd.2022.07.114","article-title":"P.66 Predicting trajectories of ambulatory function in Duchenne muscular dystrophy (DMD)","volume":"32","author":"Muntoni","year":"","journal-title":"Neuromuscul. Disord."},{"key":"B24","doi-asserted-by":"publisher","first-page":"271","DOI":"10.1016\/j.nmd.2022.02.009","article-title":"Real-world and natural history data for drug evaluation in Duchenne muscular dystrophy: Suitability of the North Star ambulatory assessment for comparisons with external controls","volume":"32","author":"Muntoni","year":"","journal-title":"Neuromuscul. Disord."},{"key":"B25","doi-asserted-by":"publisher","first-page":"1386","DOI":"10.1212\/WNL.0000000000008939","article-title":"MRI vastus lateralis fat fraction predicts loss of ambulation in Duchenne muscular dystrophy","volume":"94","author":"Naarding","year":"2020","journal-title":"Neurology"},{"key":"B26","doi-asserted-by":"publisher","first-page":"375","DOI":"10.1089\/hum.2019.255","article-title":"Dose-escalation study of systemically delivered rAAVrh74.MHCK7.micro-dystrophin in the mdx mouse model of Duchenne muscular dystrophy","volume":"32","author":"Potter","year":"2021","journal-title":"Hum. Gen. Ther."},{"key":"B27","doi-asserted-by":"publisher","first-page":"79","DOI":"10.1186\/s13023-017-0631-3","article-title":"The burden, epidemiology, costs and treatment for Duchenne muscular dystrophy: An evidence review","volume":"12","author":"Ryder","year":"2017","journal-title":"Orphanet J. Rare Dis."},{"key":"B28","doi-asserted-by":"publisher","first-page":"14793","DOI":"10.1128\/JVI.79.23.14793-14803.2005","article-title":"Characterization of adeno-associated virus genomes isolated from human tissues","volume":"79","author":"Schnepp","year":"2005","journal-title":"J. Virol."},{"key":"B29","doi-asserted-by":"publisher","first-page":"250","DOI":"10.1002\/mus.24163","article-title":"Cooperative international neuromuscular research group Duchenne natural history study demonstrates insufficient diagnosis and treatment of cardiomyopathy in Duchenne muscular dystrophy","volume":"50","author":"Spurney","year":"2014","journal-title":"Muscle Nerve"},{"key":"B30","doi-asserted-by":"publisher","first-page":"837","DOI":"10.3390\/genes11080837","article-title":"Therapeutic strategies for Duchenne muscular dystrophy: An update","volume":"11","author":"Sun","year":"2020","journal-title":"Genes."},{"key":"B31","doi-asserted-by":"publisher","first-page":"1811","DOI":"10.1212\/WNL.0000000000004570","article-title":"A phase 3 randomized placebo-controlled trial of tadalafil for Duchenne muscular dystrophy","volume":"89","author":"Victor","year":"2017","journal-title":"Neurology"},{"key":"B32","doi-asserted-by":"publisher","first-page":"778","DOI":"10.3390\/pharmaceutics15030778","article-title":"Recent trends in antisense therapies for Duchenne muscular dystrophy","volume":"15","author":"Wilton-Clark","year":"2023","journal-title":"Pharmaceutics"}],"container-title":["Frontiers in Cell and Developmental Biology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcell.2023.1167762\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,7,11]],"date-time":"2023-07-11T09:24:58Z","timestamp":1689067498000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcell.2023.1167762\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,7,11]]},"references-count":32,"alternative-id":["10.3389\/fcell.2023.1167762"],"URL":"https:\/\/doi.org\/10.3389\/fcell.2023.1167762","relation":{},"ISSN":["2296-634X"],"issn-type":[{"value":"2296-634X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,7,11]]},"article-number":"1167762"}}