Document is current

Article History

Received: 10 September 2025

Accepted: 12 December 2025

First Online: 10 January 2026

Declarations

:

: Jerry R. Mendell’s affiliation at the time of part 1 of EMBARK was Center for Gene Therapy, Nationwide Children’s Hospital, Columbus, OH, USA (currently employed by Sarepta Therapeutics, Inc.); Jerry R. Mendell’s affiliation at the time of part 2 of EMBARK and current affiliation is Sarepta Therapeutics, Inc., Cambridge, MA, USA. Jerry R. Mendell received study funding from Sarepta Therapeutics, Inc. while at Nationwide Children’s Hospital at the time of the study and is currently an employee of Sarepta Therapeutics, Inc. Jerry R. Mendell is a co-inventor of AAVrh74.MHCK7.micro-dys technology. Francesco Muntoni has received honoraria and grants from Sarepta Therapeutics, Inc. for participating at symposia and advisory boards and is involved as an investigator in Sarepta Therapeutics, Inc. clinical trials. He reports participation in advisory boards for Novartis, F. Hoffmann-La Roche Ltd, Edgewise Therapeutics, Dyne Therapeutics, Pfizer, PTC Therapeutics, and Italfarmaco. Craig M. McDonald reports grants from Capricor Therapeutics, Catabasis, Edgewise Therapeutics, Epirium Bio, Italfarmaco, Pfizer, PTC Therapeutics, Santhera Pharmaceuticals, and Sarepta Therapeutics, Inc. and has a consultancy/advisory role with Biomarin, Capricor Therapeutics, Catalyst, Edgewise Therapeutics, Italfarmaco, PTC Therapeutics, F. Hoffmann-La Roche Ltd., Santhera Pharmaceuticals and Sarepta Therapeutics, Inc. He has received honoraria from PTC Therapeutics and Sarepta Therapeutics, Inc. Eugenio M. Mercuri has received fees from AveXis, Biogen, and F. Hoffmann-La Roche Ltd. Emma Ciafaloni has received honoraria from Sarepta Therapeutics, Inc. for participating on advisory boards and research and/or grant support from the Centers for Disease Control and Prevention, CureSMA, the Muscular Dystrophy Association, the National Institutes of Health, Orphazyme, the Patient-Centered Outcomes Research Institute, Parent Project Muscular Dystrophy, PTC Therapeutics, Santhera Pharmaceuticals, Sarepta Therapeutics, Inc., and the US Food and Drug Administration. Hirofumi Komaki has received grants from Sarepta Therapeutics, Inc., Pfizer, PTC Therapeutics, Taiho Pharmaceutical Co., Ltd., Chugai Pharmaceutical Co., Nippon Shinyaku Co., Ltd., and Kaneka Corporation. Hirofumi Komaki has received fees from Sarepta Therapeutics, Inc., Pfizer, PTC Therapeutics, Chugai Pharmaceutical Co., Nippon Shinyaku Co., and Kaneka Corporation. Carmen Leon-Astudillo is an investigator in Sarepta Therapeutics, Inc. clinical trials and a sub-investigator in studies sponsored by Pfizer, SolidBioSciences, Edgewise Therapeutics, Italfarmaco, and Genentech/Roche. Andrés Nascimento has received fees from AveXis, Biogen, and F. Hoffmann-La Roche Ltd. Crystal Proud participates on an advisory board and is a consultant for Biogen, Sarepta Therapeutics, Inc., AveXis/Novartis Gene Therapies, Genentech/Roche, and Scholar Rock; serves as a speaker for Biogen; and is a principal investigator of studies sponsored by AveXis/Novartis Gene Therapies, AMO Pharma, Astellas, Biogen, CSL Behring, Fibrogen, PTC Therapeutics, Pfizer, Sarepta Therapeutics, Inc., and Scholar Rock. Ulrike Schara-Schmidt has received honoraria for counseling and participating in invited talks from Sarepta Therapeutics, Inc., and F. Hoffmann-La Roche Ltd. Aravindhan Veerapandiyan has a consultancy/advisory role with AMO Pharma, AveXis, Biogen, Edgewise Therapeutics, FibroGen, Novartis, Pfizer, PTC Therapeutics, Sarepta Therapeutics, Inc., UCB Pharma, Catalyst, and Scholar Rock; has received research funding from AMO Pharma, Capricor Therapeutics, Edgewise Therapeutics, FibroGen, the Muscular Dystrophy Association, Novartis, Parent Project Muscular Dystrophy, Pfizer, RegenxBio, and Sarepta Therapeutics, Inc.; and has other relationship(s) with MedLink Neurology for editorial services. Craig M. Zaidman has received research support from Biogen and Novartis and has served on an advisory board for Sarepta Therapeutics, Inc. Matthew Furgerson, Kai Ding, Preeti Singh, Rachael Potter, and Damon R. Asher are employees of Sarepta Therapeutics, Inc. and may have stock options. Kai Ding’s affiliation at the time of part 1 of EMBARK was Sarepta Therapeutics, Inc., Cambridge, MA, USA; Kai Ding is no longer employed by Sarepta Therapeutics, Inc. Alexander P. Murphy, Carol Reid, Gregory Hooper and Carmen O. Torre are employees of Roche Products Ltd and may have stock options in F. Hoffmann-La Roche Ltd. Marianna Manfrini is an employee of F. Hoffmann-La Roche Ltd and may have stock options. Louise R. Rodino-Klapac is an employee of Sarepta Therapeutics, Inc. and may have stock options. In addition, she is a co-inventor of AAVrh74.MHCK7.micro-dys technology.

: The EMBARK study design, including patient selection, ethics declarations (including a full list of institutional review boards and ethics committees), and descriptions of the gene therapy, has been previously published in full [ ]. This trial was conducted in compliance with Good Clinical Practice guidelines and the Declaration of Helsinki. The institutional review board and ethics committee at each site approved the trial protocol and all amendments. Details of all institutional review boards and ethics committees are available in the Supplementary Material. Upon reasonable request, the trial protocol is available from the corresponding author. The study’s primary analysis was carried out after all patients completed part 1 and these findings have been published [ ]. All authors were involved in the study design, data collection, analyses, and interpretation, as well as the writing, reviewing, and approval of the manuscript and jointly agreed to its publication [ ]. The sponsor was responsible for confirming the final trial design, protocol, and conduct, along with database maintenance, data analyses, and accuracy of the data [ ]. All authors collected and had full access to the data, and attested to their accuracy and completeness in accordance with the trial protocol [ ]. Parent(s)/legal guardian(s) provided informed consent and, when applicable, patients’ assent was obtained. Safety, efficacy, data quality, and study integrity continue to be monitored by an independent data monitoring committee [ ].