Consensus recommendations and considerations for the delivery and monitoring of gene therapy in patients with Duchenne muscular dystrophy

Jodi M Wolff¹, Nora Capocci², Evrim Atas², Diana X Bharucha-Goebel³, John F Brandsema⁴, Russell J Butterfield⁵, Christina B Chadwick⁶, Manuela Corti⁷, Thomas O Crawford⁸, Linda Cripe⁹, John W Day¹⁰, Tina Duong¹⁰, Mai K ElMallah¹¹, Kevin M Flanigan¹², Lindsey A George¹³, Natalie L Goedeker¹⁴, Erica Goude¹⁵, Sharon Hesterlee², Brian Lin², Natalie K Katz¹¹, Susan E Matesanz⁴, Craig McDonald¹⁵, Elizabeth M McNally¹⁶, Claudia Mercado-Rodriguez⁷, Deipanjan Nandi¹⁷, Julie A Parsons¹⁸, Crystal Proud¹⁹, Leigh Ramos-Platt²⁰, Angela Lek², Stephanie M Salabarria⁷, Eric Camino¹, Rachel Schrader¹, Erin Shea¹¹, Richard Shell⁹, Perry B Shieh²¹, Jonathan H Soslow²², Jane B Taylor²³, Aravindhan Veerapandiyan²⁴, Chet Villa²⁵, Michele L Yang²⁴, Craig M Zaidman¹⁴, Carmen Leon-Astudillo⁷, Barry J Byrne²⁶

Affiliations

¹ Parent Project Muscular Dystrophy, USA.
² Muscular Dystrophy Association, USA.
³ Neuromuscular and Neurogenetic Disorders of Childhood, NINDS/NIH, Bethesda, MD, USA, Division of Neurology, Children's National Hospital, WA, DC, USA.
⁴ Division of Neurology, Children's Hospital of Philadelphia, Perelman School of Medicine, University of Pennsylvania, PA, USA.
⁵ Department of Pediatric Neurology, University of Utah, Salt Lake City, UT, USA.
⁶ Department of Pediatrics, University of Florida College of Medicine, Gainesville, FL, USA.
⁷ Department of Pediatrics, University of Florida College of Medicine, Gainesville, FL, USA; Powell Gene Therapy Center, University of Florida College of Medicine, Gainesville, FL, USA.
⁸ Department of Pediatrics, Johns Hopkins University, Baltimore, MD, USA.
⁹ Department of Pediatrics and Neurology, Nationwide Children's Hopsital, Columbus, OH, USA.
¹⁰ Department of Neurology, Stanford University, Stanford, CA, USA.
¹¹ Department of Pediatrics, School of Medicine, Duke University, Durham, NC, USA.
¹² Department of Pediatrics and Neurology, Nationwide Children's Hopsital, Columbus, OH, USA; Center for Gene Therapy, Nationwide Children's Hospital, Columbus, OH, USA.
¹³ Department of Pediatrics, Children's Hospital of Philadelphia, Perelman School of Medicine, University of Pennsylvania, Philadelphia PA, USA.
¹⁴ Department of Neurology, Washington University in St. Louis School of Medicine, St. Louis, MO, USA.
¹⁵ Department of Physical Medicine and Rehabilitation, University of California Davis School of Medicine, Sacramento, CA, USA.
¹⁶ Center for Genetic Medicine, Bluhm Cardiovascular Institute, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
¹⁷ The Heart Center, Nationwide Children's Hospital, Columbus, OH, USA.
¹⁸ Children's Hospital Colorado, University of Colorado School of Medicine, Aurora, CO, USA.
¹⁹ Children's Hospital of the King's Daughters, Norfolk, VA, USA.
²⁰ Department of Pediatrics, Keck School of Medicine, University of Southern California and Children's Hospital of Los Angeles, Los Angeles, CA, USA.
²¹ Department of Pediatrics, University of California, Los Angeles, CA USA.
²² Division of Pediatric Cardiology, Vanderbilt University Medical Center, Nashville, TN, USA.
²³ Department of Pediatrics, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
²⁴ Department of Pediatrics, University of Arkansas for Medical Sciences, Arkansas Children's Hospital, Little Rock, AR, USA.
²⁵ The Heart Institute, Department of Pediatrics, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.
²⁶ Department of Pediatrics, University of Florida College of Medicine, Gainesville, FL, USA; Powell Gene Therapy Center, University of Florida College of Medicine, Gainesville, FL, USA. Electronic address: Barry.byrne@ufl.edu.

PMID: 41005046
DOI: 10.1016/j.nmd.2025.106208

Review

Consensus recommendations and considerations for the delivery and monitoring of gene therapy in patients with Duchenne muscular dystrophy

Jodi M Wolff et al. Neuromuscul Disord. 2025.

. 2025 Aug 23:54:106208.

doi: 10.1016/j.nmd.2025.106208. Online ahead of print.

Authors

Affiliations

¹ Parent Project Muscular Dystrophy, USA.
² Muscular Dystrophy Association, USA.
³ Neuromuscular and Neurogenetic Disorders of Childhood, NINDS/NIH, Bethesda, MD, USA, Division of Neurology, Children's National Hospital, WA, DC, USA.
⁴ Division of Neurology, Children's Hospital of Philadelphia, Perelman School of Medicine, University of Pennsylvania, PA, USA.
⁵ Department of Pediatric Neurology, University of Utah, Salt Lake City, UT, USA.
⁶ Department of Pediatrics, University of Florida College of Medicine, Gainesville, FL, USA.
⁷ Department of Pediatrics, University of Florida College of Medicine, Gainesville, FL, USA; Powell Gene Therapy Center, University of Florida College of Medicine, Gainesville, FL, USA.
⁸ Department of Pediatrics, Johns Hopkins University, Baltimore, MD, USA.
⁹ Department of Pediatrics and Neurology, Nationwide Children's Hopsital, Columbus, OH, USA.
¹⁰ Department of Neurology, Stanford University, Stanford, CA, USA.
¹¹ Department of Pediatrics, School of Medicine, Duke University, Durham, NC, USA.
¹² Department of Pediatrics and Neurology, Nationwide Children's Hopsital, Columbus, OH, USA; Center for Gene Therapy, Nationwide Children's Hospital, Columbus, OH, USA.
¹³ Department of Pediatrics, Children's Hospital of Philadelphia, Perelman School of Medicine, University of Pennsylvania, Philadelphia PA, USA.
¹⁴ Department of Neurology, Washington University in St. Louis School of Medicine, St. Louis, MO, USA.
¹⁵ Department of Physical Medicine and Rehabilitation, University of California Davis School of Medicine, Sacramento, CA, USA.
¹⁶ Center for Genetic Medicine, Bluhm Cardiovascular Institute, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
¹⁷ The Heart Center, Nationwide Children's Hospital, Columbus, OH, USA.
¹⁸ Children's Hospital Colorado, University of Colorado School of Medicine, Aurora, CO, USA.
¹⁹ Children's Hospital of the King's Daughters, Norfolk, VA, USA.
²⁰ Department of Pediatrics, Keck School of Medicine, University of Southern California and Children's Hospital of Los Angeles, Los Angeles, CA, USA.
²¹ Department of Pediatrics, University of California, Los Angeles, CA USA.
²² Division of Pediatric Cardiology, Vanderbilt University Medical Center, Nashville, TN, USA.
²³ Department of Pediatrics, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
²⁴ Department of Pediatrics, University of Arkansas for Medical Sciences, Arkansas Children's Hospital, Little Rock, AR, USA.
²⁵ The Heart Institute, Department of Pediatrics, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.
²⁶ Department of Pediatrics, University of Florida College of Medicine, Gainesville, FL, USA; Powell Gene Therapy Center, University of Florida College of Medicine, Gainesville, FL, USA. Electronic address: Barry.byrne@ufl.edu.

PMID: 41005046
DOI: 10.1016/j.nmd.2025.106208

Abstract

Gene transfer therapy represents a major advancement in the treatment of patients with Duchenne muscular dystrophy (DMD). As clinical use expands, there is an urgent need for standardized, evidence and practice-informed guidelines to ensure safe and equitable delivery of this and similar products. A group of clinicians and researchers, coordinated by the Muscular Dystrophy Association and Parent Project Muscular Dystrophy, developed these consensus guidelines to outline recommendations for patient selection, institutional readiness, monitoring, and adverse event management, particularly in the first three months after treatment. This document emphasizes the importance of experienced multidisciplinary teams, real-time safety surveillance, and transparent reporting to support patient safety and clinician decision-making after treatment. While the Food and Drug Administration has approved only one gene therapy product for the treatment of patients with DMD, these recommendations may potentially apply to other products in clinical development. Currently, significant knowledge gaps remain regarding long-term safety, durability, and optimal timing of dosing, particularly for patients with advanced disease. Researchers do not fully understand how combination therapies and genetic background may impact the response to gene therapy. To address these gaps, ongoing real-world data collection, cross-center collaboration, and flexible adaptation of clinical protocols are essential. While these guidelines are based primarily on clinical expertise rather than well-established evidence, the guideline provides a foundation to support administration of gene therapy for patients with DMD. As the field evolves, continued refinement will be essential to maximize benefit, reduce risk, and inform future standards of care.

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Conflict of interest statement

Declaration of competing interest Barry J. Byrne: BJB receives funding from R01HD052682, R01AR056973, UG3NS137533, U01NS116752, P50-AR-052646, is an advisor to Rocket Pharma and Tenaya Therapeutics as well as a member of the Medical Advisory Board and Board of Directors of the Muscular Dystrophy Association. Carmen Leon-Astudillo: CLA is a site investigator of studies sponsored by Genentech/Roche, Biohaven, Sarepta Therapeutics, Edgewise, Regenxbio. Diana Bharucha-Goebel: DBG is a member of the MDA medical advisory committee. Elizabeth M. McNally: EMM consults for or has consulted for Amgen, Cytokinetics, PepGen, Tenaya Therapeutics, and Novartis. EMM is a founder of Ikaka Therapeutics and co-founder of Kardigan; receives funding from NIH HD119693, HL167813, and NS047726, as well as Parent Project Muscular Dystrophy and is a member of the Board of Directors of the Muscular Dystrophy Association. John F. Brandsema: JFB is a consultant for Alexion, Argenx, Audentes, AveXis/ Novartis, Biogen, CSL Behring, Cytokinetics, Dyne, Edgewise, Entrada, Fibrogen, Genentech/Roche, ITF, Ipsen, Janssen, Marathon, Mesoblast, Momenta, NS Pharma, Percheron, Pfizer, PTC Therapeutics, Sarepta, Scholar Rock, Takeda, WaVe; is a medical advisory council member for Cure SMA; is a site investigator for clinical trials with Alexion, Astellas, AveXis/Novartis, Biogen, Biohaven, Catabasis, CSL Behring, Cytokinetics, Dyne, Fibrogen, Genentech/Roche, Ionis, Italfarmaco, Lilly, Janssen, Pfizer, PTC Therapeutics, Sarepta, Scholar Rock, Summit, UCB, WaVe. John W. Day: JWD reports grants from Astellas Gene Therapies, CureSMA, Muscular Dystrophy Association; Myotonic Dystrophy Foundation, Novartis, Roche Pharmaceuticals, RegenxBio, Sanofi-Genzyme and Sarepta Therapeutics; served on scientific advisory boards, data safety and management boards, advisory committees or consulted with Affinia Therapeutics; Audentes, Kate Therapeutics, Novartis, Pfizer, Roche/Genentech Pharmaceuticals, Sanofi, Sarepta Therapeutics, Solid Biosciences, Vertex Pharmaceuticals. Jonathan H. Soslow: JHS has consulted for Sarepta Therapeutics and is part of their Real World Evidence Steering Committee; and has consulted for the following in the last 3 years, though they are not directly related to this manuscript: Boehringer Ingelheim, Capricor, Dyne, Immunoforge, NS Pharma, and Wave; receives funding from the Food and Drug Administration Orphan Products Grant R01FD006649, R01HL167969, and Parent Project Muscular Dystrophy. Julie A. Parsons: JAP has served as an advisor for Biogen, Genentech, Novartis, Dyne, Ultragenyx, Astellas, Keros, Bridge Bio. I have been a PI on clinical trials for Biogen, Genentech, Novartis, Biohaven, Scholar Rock, PTC Therapeutics in the last 2 years. JAP is on the Medical Advisory Committee for Cure SMA. Leigh Ramos-Platt: LRP is a PI for Sarepta, Capricor, Fibrogen, PTC in the past 3 years and has served on advisory boards for Sarepta Therapeutics, Solid Biosciences, IFT and Catalyst in the past 3 years. Lindsey George: LG is on the Scientific Advisory Board of Form Bio, is a consultant for CSL Behring, Myogene, Pfizer, Regeneron and Spark Therapeutics and receives licensing fees and research support from Roche, and recieves funding from R01HL179221. Mai K. ElMallah: MKE receives funding from R01HL171282. Manuela Corti: MC receives funding U01-NS116752–01A1 and R01HD052682. Michele L. Yang: MLY is a site PI for studies sponsored by NS pharma, Regenxbio, Sarepta Therapeuics and Edgewise. Natalie Goedeker: NG has been a paid advisor for Sarepta within the last 3 years. NG is a member of the Speaker's Bureau for ITF Therapeutics, and receives consulting fees for Precision Biosciences. Richard Shell: RS is a consultant for Astellas Pharmaceuticals and study adjudicator for Biogen. Neither of these are related to the topic in this manuscript. Russel J. Butterfield: RJB is a scientific advisor for Novartis, Scholar rock, Sarepta, and Precision Bio and received grant funding from Ionis Pharmaceuticals. Susan E. Matesanz: SEM serves on advisory boards for Sarepta Therapeutics, Avidity, Novartis and is a site investigator for Dyne, Genentech/Roche, Pfizer and Sarepta Therapeutics.

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Consensus recommendations and considerations for the delivery and monitoring of gene therapy in patients with Duchenne muscular dystrophy

Affiliations

Consensus recommendations and considerations for the delivery and monitoring of gene therapy in patients with Duchenne muscular dystrophy

Authors

Affiliations

Abstract

Conflict of interest statement

Publication types