{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T13:42:33Z","timestamp":1790516553724,"version":"4.1.0"},"reference-count":36,"publisher":"Springer Science and Business Media LLC","issue":"8","license":[{"start":{"date-parts":[[2022,4,8]],"date-time":"2022-04-08T00:00:00Z","timestamp":1649376000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2022,4,8]],"date-time":"2022-04-08T00:00:00Z","timestamp":1649376000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/100004319","name":"Pfizer","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100004319","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["J Neurol"],"published-print":{"date-parts":[[2022,8]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Duchenne muscular dystrophy (DMD) is a progressive, neuromuscular disorder caused by mutations in the <jats:italic>DMD<\/jats:italic> gene that results in a lack of functional dystrophin protein. Herein, we report the use of quantitative magnetic resonance imaging (MRI) measures as biomarkers in the context of a multicenter phase 2, randomized, placebo-controlled clinical trial evaluating the myostatin inhibitor domagrozumab in ambulatory boys with DMD (<jats:italic>n<\/jats:italic>\u2009=\u2009120 aged 6 to\u2009&lt;\u200916\u00a0years). MRI scans of the thigh to measure muscle volume, muscle volume index (MVI), fat fraction, and T2 relaxation time were obtained at baseline and at weeks 17, 33, 49, and 97 as per protocol. These quantitative MRI measurements appeared to be sensitive and objective biomarkers for evaluating disease progression, with significant changes observed in muscle volume, MVI, and T2 mapping measures over time. To further explore the utility of quantitative MRI measures as biomarkers to inform longer term functional changes in this cohort, a regression analysis was performed and demonstrated that muscle volume, MVI, T2 mapping measures, and fat fraction assessment were significantly correlated with longer term changes in four-stair climb times and North Star Ambulatory Assessment functional scores. Finally, less favorable baseline measures of MVI, fat fraction of the muscle bundle, and fat fraction of lean muscle were significant risk factors for loss of ambulation over a 2-year monitoring period. These analyses suggest that MRI can be a valuable tool for use in clinical trials and may help inform future functional changes in DMD.<\/jats:p><jats:p>Trial registration: ClinicalTrials.gov identifier, NCT02310763; registered December 2014.<\/jats:p>","DOI":"10.1007\/s00415-022-11084-0","type":"journal-article","created":{"date-parts":[[2022,4,8]],"date-time":"2022-04-08T17:02:50Z","timestamp":1649437370000},"page":"4421-4435","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":26,"title":["Quantitative magnetic resonance imaging measures as biomarkers of disease progression in boys with Duchenne muscular dystrophy: a phase 2 trial of domagrozumab"],"prefix":"10.1007","volume":"269","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5351-3828","authenticated-orcid":false,"given":"Sarah P.","family":"Sherlock","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeffrey","family":"Palmer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kathryn R.","family":"Wagner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hoda Z.","family":"Abdel-Hamid","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Enrico","family":"Bertini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cuixia","family":"Tian","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean K.","family":"Mah","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Kostera-Pruszczyk","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesco","family":"Muntoni","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michela","family":"Guglieri","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John F.","family":"Brandsema","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eugenio","family":"Mercuri","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Russell J.","family":"Butterfield","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Craig M.","family":"McDonald","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lawrence","family":"Charnas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shannon","family":"Marraffino","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2022,4,8]]},"reference":[{"key":"11084_CR1","doi-asserted-by":"publisher","first-page":"320","DOI":"10.1002\/nbm.2851","volume":"26","author":"I Arpan","year":"2013","unstructured":"Arpan I, Forbes SC, Lott DJ et al (2013) T(2) mapping provides multiple approaches for the characterization of muscle involvement in neuromuscular diseases: a cross-sectional study of lower leg muscles in 5\u201315-year-old boys with Duchenne muscular dystrophy. NMR Biomed 26:320\u2013328. https:\/\/doi.org\/10.1002\/nbm.2851","journal-title":"NMR Biomed"},{"key":"11084_CR2","doi-asserted-by":"publisher","first-page":"e897","DOI":"10.1212\/WNL.0000000000009012","volume":"94","author":"AM Barnard","year":"2020","unstructured":"Barnard AM, Willcocks RJ, Triplett WT et al (2020) MR biomarkers predict clinical function in Duchenne muscular dystrophy. Neurology 94:e897\u2013e909. https:\/\/doi.org\/10.1212\/WNL.0000000000009012","journal-title":"Neurology"},{"key":"11084_CR3","doi-asserted-by":"publisher","first-page":"484","DOI":"10.1002\/cpdd.386","volume":"7","author":"I Bhattacharya","year":"2018","unstructured":"Bhattacharya I, Pawlak S, Marraffino S et al (2018) Safety, tolerability, pharmacokinetics, and pharmacodynamics of domagrozumab (PF-06252616), an antimyostatin monoclonal antibody, in healthy subjects. Clin Pharmacol Drug Dev 7:484\u2013497. https:\/\/doi.org\/10.1002\/cpdd.386","journal-title":"Clin Pharmacol Drug Dev"},{"key":"11084_CR4","doi-asserted-by":"publisher","first-page":"347","DOI":"10.1016\/S1474-4422(18)30025-5","volume":"17","author":"DJ Birnkrant","year":"2018","unstructured":"Birnkrant DJ, Bushby K, Bann CM et al (2018) 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","journal-title":"Lancet Neurol"},{"key":"11084_CR5","doi-asserted-by":"publisher","first-page":"251","DOI":"10.1016\/S1474-4422(18)30024-3","volume":"17","author":"DJ Birnkrant","year":"2018","unstructured":"Birnkrant DJ, Bushby K, Bann CM et al (2018) Diagnosis and management of Duchenne muscular dystrophy, part 1: diagnosis, and neuromuscular, rehabilitation, endocrine, and gastrointestinal and nutritional management. Lancet Neurol 17:251\u2013267. https:\/\/doi.org\/10.1016\/S1474-4422(18)30024-3","journal-title":"Lancet Neurol"},{"key":"11084_CR6","doi-asserted-by":"publisher","first-page":"418","DOI":"10.1038\/nature01154","volume":"420","author":"S Bogdanovich","year":"2002","unstructured":"Bogdanovich S, Krag TO, Barton ER, Morris LD, Whittemore LA, Ahima RS, Khurana TS (2002) Functional improvement of dystrophic muscle by myostatin blockade. Nature 420:418\u2013421. https:\/\/doi.org\/10.1038\/nature01154","journal-title":"Nature"},{"key":"11084_CR7","volume-title":"Classification and regression trees","author":"L Breiman","year":"1984","unstructured":"Breiman L, Friedman JH, Olshen RA, Stone CJ (1984) Classification and regression trees. Wadsworth & Brooks\/Cole Advanced Books & Software, Monterey, CA"},{"key":"11084_CR8","doi-asserted-by":"publisher","unstructured":"Cai W, Chen S, Zhang D (2007) Fast and robust fuzzy c-means clustering algorithms incorporating local information for image segmentation. Pattern Recognition 40:825\u2013838. https:\/\/doi.org\/10.1016\/j.patcog.2006.07.011","DOI":"10.1016\/j.patcog.2006.07.011"},{"key":"11084_CR9","doi-asserted-by":"publisher","first-page":"982","DOI":"10.1001\/jamaneurol.2020.1264","volume":"77","author":"PR Clemens","year":"2020","unstructured":"Clemens PR, Rao VK, Connolly AM et al (2020) 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","journal-title":"JAMA Neurol"},{"key":"11084_CR10","doi-asserted-by":"publisher","first-page":"143","DOI":"10.1007\/s13539-011-0035-5","volume":"2","author":"Y Elkina","year":"2011","unstructured":"Elkina Y, von Haehling S, Anker SD, Springer J (2011) The role of myostatin in muscle wasting: an overview. J Cachexia Sarcopenia Muscle 2:143\u2013151. https:\/\/doi.org\/10.1007\/s13539-011-0035-5","journal-title":"J Cachexia Sarcopenia Muscle"},{"key":"11084_CR11","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0081302","volume":"8","author":"RS Finkel","year":"2013","unstructured":"Finkel RS, Flanigan KM, Wong B et al (2013) Phase 2a study of ataluren-mediated dystrophin production in patients with nonsense mutation Duchenne muscular dystrophy. PLoS ONE 8:e81302. https:\/\/doi.org\/10.1371\/journal.pone.0081302","journal-title":"PLoS ONE"},{"key":"11084_CR12","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0106435","volume":"9","author":"SC Forbes","year":"2014","unstructured":"Forbes SC, Willcocks RJ, Triplett WT et al (2014) Magnetic resonance imaging and spectroscopy assessment of lower extremity skeletal muscles in boys with Duchenne muscular dystrophy: a multicenter cross sectional study. PLoS ONE 9:e106435. https:\/\/doi.org\/10.1371\/journal.pone.0106435","journal-title":"PLoS ONE"},{"key":"11084_CR13","doi-asserted-by":"publisher","first-page":"e2270","DOI":"10.1212\/WNL.0000000000009233","volume":"94","author":"DE Frank","year":"2020","unstructured":"Frank DE, Schnell FJ, Akana C et al (2020) Increased dystrophin production with golodirsen in patients with Duchenne muscular dystrophy. Neurology 94:e2270\u2013e2282. https:\/\/doi.org\/10.1212\/WNL.0000000000009233","journal-title":"Neurology"},{"key":"11084_CR14","doi-asserted-by":"publisher","first-page":"607","DOI":"10.1002\/acn3.319","volume":"3","author":"C Godi","year":"2016","unstructured":"Godi C, Ambrosi A, Nicastro F et al (2016) Longitudinal MRI quantification of muscle degeneration in Duchenne muscular dystrophy. Ann Clin Transl Neurol 3:607\u2013622. https:\/\/doi.org\/10.1002\/acn3.319","journal-title":"Ann Clin Transl Neurol"},{"key":"11084_CR15","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0164684","volume":"11","author":"N Goemans","year":"2016","unstructured":"Goemans N, Vanden Hauwe M, Signorovitch J, Swallow E, Song J (2016) Individualized prediction of changes in 6-minute walk distance for patients with Duchenne muscular dystrophy. PLoS ONE 11:e0164684. https:\/\/doi.org\/10.1371\/journal.pone.0164684","journal-title":"PLoS ONE"},{"key":"11084_CR16","doi-asserted-by":"publisher","first-page":"304","DOI":"10.3348\/kjr.2010.11.3.304","volume":"11","author":"HK Kim","year":"2010","unstructured":"Kim HK, Laor T, Horn PS, Wong B (2010) Quantitative assessment of the T2 relaxation time of the gluteus muscles in children with Duchenne muscular dystrophy: a comparative study before and after steroid treatment. Korean J Radiol 11:304\u2013311. https:\/\/doi.org\/10.3348\/kjr.2010.11.3.304","journal-title":"Korean J Radiol"},{"key":"11084_CR17","doi-asserted-by":"publisher","first-page":"19371","DOI":"10.1074\/jbc.M802585200","volume":"283","author":"ZB Li","year":"2008","unstructured":"Li ZB, Kollias HD, Wagner KR (2008) Myostatin directly regulates skeletal muscle fibrosis. J Biol Chem 283:19371\u201319378. https:\/\/doi.org\/10.1074\/jbc.M802585200","journal-title":"J Biol Chem"},{"key":"11084_CR18","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1007\/978-1-4939-7374-3_1","volume":"1687","author":"JK Mah","year":"2018","unstructured":"Mah JK (2018) An overview of recent therapeutics advances for Duchenne muscular dystrophy. Methods Mol Biol 1687:3\u201317. https:\/\/doi.org\/10.1007\/978-1-4939-7374-3_1","journal-title":"Methods Mol Biol"},{"key":"11084_CR19","doi-asserted-by":"publisher","first-page":"743","DOI":"10.1093\/oxfordjournals.bja.a013586","volume":"84","author":"S Malviya","year":"2000","unstructured":"Malviya S, Voepel-Lewis T, Eldevik OP, Rockwell DT, Wong JH, Tait AR (2000) Sedation and general anaesthesia in children undergoing MRI and CT: adverse events and outcomes. Br J Anaesth 84:743\u2013748. https:\/\/doi.org\/10.1093\/oxfordjournals.bja.a013586","journal-title":"Br J Anaesth"},{"key":"11084_CR20","doi-asserted-by":"publisher","first-page":"1046","DOI":"10.1111\/dmcn.12220","volume":"55","author":"AG Mayhew","year":"2013","unstructured":"Mayhew AG, Cano SJ, Scott E, Eagle M, Bushby K, Manzur A, Muntoni F (2013) Detecting meaningful change using the North Star Ambulatory Assessment in Duchenne muscular dystrophy. Dev Med Child Neurol 55:1046\u20131052. https:\/\/doi.org\/10.1111\/dmcn.12220","journal-title":"Dev Med Child Neurol"},{"key":"11084_CR21","doi-asserted-by":"publisher","first-page":"451","DOI":"10.1016\/S0140-6736(17)32160-8","volume":"391","author":"CM McDonald","year":"2018","unstructured":"McDonald CM, Henricson EK, Abresch RT et al (2018) Long-term effects of glucocorticoids on function, quality of life, and survival in patients with Duchenne muscular dystrophy: a prospective cohort study. Lancet 391:451\u2013461. https:\/\/doi.org\/10.1016\/S0140-6736(17)32160-8","journal-title":"Lancet"},{"key":"11084_CR22","doi-asserted-by":"publisher","first-page":"343","DOI":"10.1002\/mus.23902","volume":"48","author":"CM McDonald","year":"2013","unstructured":"McDonald CM, Henricson EK, Abresch RT et al (2013) The 6-minute walk test and other endpoints in Duchenne muscular dystrophy: longitudinal natural history observations over 48 weeks from a multicenter study. Muscle Nerve 48:343\u2013356. https:\/\/doi.org\/10.1002\/mus.23902","journal-title":"Muscle Nerve"},{"key":"11084_CR23","doi-asserted-by":"publisher","first-page":"257","DOI":"10.1002\/ana.24555","volume":"79","author":"JR Mendell","year":"2016","unstructured":"Mendell JR, Goemans N, Lowes LP et al (2016) Longitudinal effect of eteplirsen versus historical control on ambulation in Duchenne muscular dystrophy. Ann Neurol 79:257\u2013271. https:\/\/doi.org\/10.1002\/ana.24555","journal-title":"Ann Neurol"},{"key":"11084_CR24","doi-asserted-by":"publisher","first-page":"e1386","DOI":"10.1212\/WNL.0000000000008939","volume":"94","author":"KJ Naarding","year":"2020","unstructured":"Naarding KJ, Reyngoudt H, van Zwet EW et al (2020) MRI vastus lateralis fat fraction predicts loss of ambulation in Duchenne muscular dystrophy. Neurology 94:e1386\u2013e1394. https:\/\/doi.org\/10.1212\/WNL.0000000000008939","journal-title":"Neurology"},{"key":"11084_CR25","doi-asserted-by":"publisher","first-page":"677","DOI":"10.1002\/jmri.21699","volume":"29","author":"V Positano","year":"2009","unstructured":"Positano V, Christiansen T, Santarelli MF, Ringgaard S, Landini L, Gastaldelli A (2009) Accurate segmentation of subcutaneous and intermuscular adipose tissue from MR images of the thigh. J Magn Reson Imaging 29:677\u2013684. https:\/\/doi.org\/10.1002\/jmri.21699","journal-title":"J Magn Reson Imaging"},{"key":"11084_CR26","doi-asserted-by":"publisher","first-page":"117","DOI":"10.1212\/WNL.0000000000008811","volume":"94","author":"J Ropars","year":"2020","unstructured":"Ropars J, Gravot F, Ben Salem D, Rousseau F, Brochard S, Pons C (2020) Muscle MRI: A biomarker of disease severity in Duchenne muscular dystrophy? A systematic review. Neurology 94:117\u2013133. https:\/\/doi.org\/10.1212\/WNL.0000000000008811","journal-title":"Neurology"},{"key":"11084_CR27","doi-asserted-by":"publisher","first-page":"79","DOI":"10.1186\/s13023-017-0631-3","volume":"12","author":"S Ryder","year":"2017","unstructured":"Ryder S, Leadley RM, Armstrong N, Westwood M, de Kock S, Butt T, Jain M, Kleijnen J (2017) The burden, epidemiology, costs and treatment for Duchenne muscular dystrophy: an evidence review. Orphanet J Rare Dis 12:79. https:\/\/doi.org\/10.1186\/s13023-017-0631-3","journal-title":"Orphanet J Rare Dis"},{"key":"11084_CR28","doi-asserted-by":"publisher","first-page":"101","DOI":"10.1002\/pri.520","volume":"17","author":"E Scott","year":"2012","unstructured":"Scott E, Eagle M, Mayhew A, Freeman J, Main M, Sheehan J, Manzur A, Muntoni F (2012) Development of a functional assessment scale for ambulatory boys with Duchenne muscular dystrophy. Physiother Res Int 17:101\u2013109. https:\/\/doi.org\/10.1002\/pri.520","journal-title":"Physiother Res Int"},{"key":"11084_CR29","doi-asserted-by":"publisher","first-page":"761","DOI":"10.2217\/bmm-2020-0801","volume":"15","author":"SP Sherlock","year":"2021","unstructured":"Sherlock SP, Zhang Y, Binks M, Marraffino S (2021) Quantitative muscle MRI biomarkers in Duchenne muscular dystrophy: cross-sectional correlations with age and functional tests. Biomark Med 15:761\u2013773. https:\/\/doi.org\/10.2217\/bmm-2020-0801","journal-title":"Biomark Med"},{"key":"11084_CR30","doi-asserted-by":"publisher","first-page":"1","DOI":"10.3390\/jpm9010001","volume":"9","author":"Y Shimizu-Motohashi","year":"2019","unstructured":"Shimizu-Motohashi Y, Komaki H, Motohashi N, Takeda S, Yokota T, Aoki Y (2019) Restoring dystrophin expression in Duchenne muscular dystrophy: current status of therapeutic approaches. J Pers Med 9:1. https:\/\/doi.org\/10.3390\/jpm9010001","journal-title":"J Pers Med"},{"key":"11084_CR31","doi-asserted-by":"publisher","first-page":"25","DOI":"10.1186\/s13395-017-0141-y","volume":"7","author":"M St Andre","year":"2017","unstructured":"St Andre M, Johnson M, Bansal PN et al (2017) A mouse anti-myostatin antibody increases muscle mass and improves muscle strength and contractility in the mdx mouse model of Duchenne muscular dystrophy and its humanized equivalent, domagrozumab (PF-06252616), increases muscle volume in cynomolgus monkeys. Skelet Muscle 7:25. https:\/\/doi.org\/10.1186\/s13395-017-0141-y","journal-title":"Skelet Muscle"},{"key":"11084_CR32","doi-asserted-by":"publisher","unstructured":"Wagner KR, Abdel-Hamid HZ, Mah JK et al (2021) Corrigendum to \"Randomized phase 2 trial and open-label extension of domagrozumab in Duchenne muscular dystrophy\" [Neuromuscular Disorders, Vol. 30 (6) 2020, 492\u2013502]. Neuromuscul Disord 31:167\u2013168. https:\/\/doi.org\/10.1016\/j.nmd.2021.01.001","DOI":"10.1016\/j.nmd.2021.01.001"},{"key":"11084_CR33","doi-asserted-by":"publisher","first-page":"492","DOI":"10.1016\/j.nmd.2020.05.002","volume":"30","author":"KR Wagner","year":"2020","unstructured":"Wagner KR, Abdel-Hamid HZ, Mah JK et al (2020) Randomized phase 2 trial and open-label extension of domagrozumab in Duchenne muscular dystrophy. Neuromuscul Disord 30:492\u2013502. https:\/\/doi.org\/10.1016\/j.nmd.2020.05.002","journal-title":"Neuromuscul Disord"},{"key":"11084_CR34","doi-asserted-by":"publisher","first-page":"722","DOI":"10.1097\/wco.0000000000000739","volume":"32","author":"MA Waldrop","year":"2019","unstructured":"Waldrop MA, Flanigan KM (2019) Update in Duchenne and Becker muscular dystrophy. Curr Opin Neurol 32:722\u2013727. https:\/\/doi.org\/10.1097\/wco.0000000000000739","journal-title":"Curr Opin Neurol"},{"key":"11084_CR35","doi-asserted-by":"publisher","first-page":"393","DOI":"10.1016\/j.nmd.2013.12.012","volume":"24","author":"RJ Willcocks","year":"2014","unstructured":"Willcocks RJ, Arpan IA, Forbes SC et al (2014) Longitudinal measurements of MRI-T2 in boys with Duchenne muscular dystrophy: effects of age and disease progression. Neuromuscul Disord 24:393\u2013401. https:\/\/doi.org\/10.1016\/j.nmd.2013.12.012","journal-title":"Neuromuscul Disord"},{"key":"11084_CR36","doi-asserted-by":"publisher","first-page":"359","DOI":"10.1109\/83.661186","volume":"7","author":"C Xu","year":"1998","unstructured":"Xu C, Prince JL (1998) Snakes, shapes, and gradient vector flow. IEEE Trans Image Process 7:359\u2013369. https:\/\/doi.org\/10.1109\/83.661186","journal-title":"IEEE Trans Image Process"}],"container-title":["Journal of Neurology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00415-022-11084-0.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s00415-022-11084-0\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00415-022-11084-0.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,7,18]],"date-time":"2022-07-18T16:33:07Z","timestamp":1658161987000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s00415-022-11084-0"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,4,8]]},"references-count":36,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2022,8]]}},"alternative-id":["11084"],"URL":"https:\/\/doi.org\/10.1007\/s00415-022-11084-0","relation":{},"ISSN":["0340-5354","1432-1459"],"issn-type":[{"value":"0340-5354","type":"print"},{"value":"1432-1459","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,4,8]]},"assertion":[{"value":"23 November 2021","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"11 March 2022","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"12 March 2022","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"8 April 2022","order":4,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"SPS, JP, LC, and SM are employees of and hold stock or stock options in Pfizer. KRW is an employee of and holds stock in F. Hoffmann-La Roche Ltd. HZAH has received research support from and served on advisory boards for Sarepta Therapeutics, Biogen, NS Pharma, and AveXis\/Novartis. EB has served on scientific advisory boards for Sarepta Therapeutics, Biogen, AveXis, and PTC Therapeutics. CT has been site investigator for clinical trials with Pfizer, AveXis\/Novartis, Catabasis, WaVe, Roche, PTC Therapeutics, Fibrogen, Capricor, Santhera Therapeutics, Sarepta Therapeutics, and Summit. JKM has received research support for clinical trials from Pfizer, Italfarmaco, Sarepta Therapeutics, Catabasis, Roche, Biogen, Novartis, NS Pharma, PTC Therapeutics, and ReveraGen; and consultant fees from Roche and Biogen. AKP has served on advisory boards for or received consultant fees from Pfizer, Biogen, AveXis, Novartis, PTC Therapeutics, and Roche; and received research support from Biogen, Sanofi-Aventis, CSL Behring, Kedrion, and Shire. FM is a member of the Pfizer Rare Disease Scientific Advisory Board; has received grant support from Biogen and Sarepta Therapeutics; and has received consultant fees and\/or speakers\u2019 honoraria from Novartis, Biogen, Roche, Dyne Therapeutics, and PTC Therapeutics. MG has served as chair for a ReveraGen study; collaborated on research with ReveraGen and Sarepta Therapeutics; acted as principal investigator for clinical trials sponsored by Pfizer, Italfarmaco, Santhera Therapeutics, ReveraGen, Dynacure, Roche, PTC Therapeutics, and Summit; participated in advisory boards for Pfizer, NS Pharma, and Dyne (consultancies through Newcastle University); and preformed consultancy work (speaker) for Sarepta Therapeutics. JFB has been site investigator for clinical trials with Alexion, AveXis\/Novartis, Biogen, Catabasis, CSL, Behring, Cytokinetics, Fibrogen, Ionis, Pfizer, PTC Therapeutics, Sarepta Therapeutics, Summit, and WaVe; consultant for Audentes, AveXis\/Novartis, Biogen, Cytokinetics, Genentech, Marathon, Momenta, NS Pharma, PTC Therapeutics, Sarepta Therapeutics, Scholar Rock, and WaVe; speaker for AveXis\/Novartis and Biogen; and medical advisory council member for Cure SMA. EM has served on advisory boards for Sarepta Therapeutics, Santhera Therapeutics, PTC Therapeutics, Pfizer, NS Pharma, and Roche. RJB has received funding via contracts for clinical trials from AveXis\/Novartis, PTC Therapeutics, Sarepta Therapeutics, Pfizer, and Biogen; and served on scientific advisory boards for Sarepta Therapeutics, Biogen, AveXis\/Novartis, and Pfizer. CMM has acted as a consultant on clinical trials for Astellas, Avidity Biosciences, BioMarin, Capricor Therapeutics, Catabasis Pharmaceuticals, Edgewise Therapeutics, Eli Lilly and Company, Entrada Therapeutics, Epirium Bio (formerly Cardero Therapeutics), FibroGen, Gilead, Hoffmann-La Roche, Italfarmaco, Pfizer, PTC Therapeutics, Santhera Pharmaceuticals, and Sarepta Therapeutics; and received research support for clinical trials from BioMarin, Capricor Therapeutics, Eli Lilly and Company, Italfarmaco, Pfizer, PTC Therapeutics, Hoffmann-La Roche, Santhera Pharmaceuticals, and Sarepta Therapeutics.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflicts of interest"}},{"value":"The original phase 2 trial was conducted in accordance with legal and regulatory requirements, as well as the general principles set forth in the International Ethical Guidelines for Biomedical Research Involving Human Subjects, guidelines for Good Clinical Practice, and the Declaration of Helsinki. The protocols, any amendments, and informed consent\/assent documents were approved by the institutional review board or ethics committee at each study center.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval"}},{"value":"A parent or legal guardian provided written informed consent prior to any study-specific activity that was performed.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent to participate"}},{"value":"Not applicable.","order":5,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent to publish"}}]}}