Limb-Girdle Muscular Dystrophy Scientific Workshop: A Multistakeholder Discussion Focused on Charting the Path Forward for Drug Development
- PMID: 40756520
- PMCID: PMC12314789
- DOI: 10.1212/CPJ.0000000000200496
Limb-Girdle Muscular Dystrophy Scientific Workshop: A Multistakeholder Discussion Focused on Charting the Path Forward for Drug Development
Abstract
Limb-girdle muscular dystrophy (LGMD) refers to a group of muscular dystrophies that generally result in weakness and loss of limb-girdle muscles, leading to severe disability and early mortality due to cardiac and respiratory complications. Heterogeneity across and within individual LGMD subtypes in addition to variability in progression rates presents significant challenges to traditional drug development approaches for these diseases. In an effort to discuss these challenges, as well as opportunities in support of advancing drug development for LGMD, on February 8, 2024, The Speak Foundation assembled a multistakeholder group consisting of academic medical experts, patients and caregivers, patient advocacy organizations, senior leaders from the US Food and Drug Administration, and commercial drug developers. This review will provide an overview of the broad range of topics discussed at the workshop, including LGMD pathophysiology, natural history studies, clinical outcomes, patient-focused drug development, surrogate end points, the Accelerated Approval pathway, and future directions for LGMD drug development.
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Conflict of interest statement
M.P. Wicklund has served on advisory boards for Amicus Therapeutics, Edgewise Therapeutics, Lupin Pharmaceuticals, Sarepta Therapeutics, and UCB Pharmaceuticals; contributed to educational programs at VuMedi, Med Learning Group, Muscular Dystrophy Association, and Oculopharyngeal Muscular Dystrophy Association; and received research funding from Catalyst Pharmaceuticals, Fulcrum Therapeutics, ML Bio Solutions, and Sarepta Therapeutics. L.N. Alfano has served on advisory boards for Bayer AG/Asklepios BioPharmaceutical, Dyne Therapeutics, and Sarepta Therapeutics; received salary support for training and quality control programs for Astellas Gene Therapies and Sarepta Therapeutics through Nationwide Children's Hospital; received consulting fees for training and quality control services performed through ATOM International, Ltd; received royalties from licensed intellectual property from Glycomine, Inc; Insmed Gene Therapies, LLC; and Sarepta Therapeutics; and received research funding from Ultragenyx Pharmaceutical Inc. N.E. Johnson has received grant funding from National Institute of Neurological Disorders and Stroke (R01NS104010, U01NS124974), National Center for Advancing Translational Sciences (R21TR003184), Centers for Disease Control and Prevention (U01DD001242), and the FDA (7R01FD006071). He receives royalties from the Congenital and Childhood Myotonic Dystrophy Health Index and the Charcot-Marie-Tooth Health Index. He receives research funds from Novartis, Takeda, PepGen, Sanofi Genzyme, Dyne, Vertex Pharmaceuticals, Fulcrum Therapeutics, AskBio, ML Bio Solutions, and Sarepta. He has provided consultation for Arthex, Juvena, Rgenta, PepGen, AMO Pharma, Takeda, Design, Dyne, AskBio, Avidity, ML Bio Solutions, and Vertex Pharmaceuticals. He has equity interests in Myogene therapeutics and angle therapeutics. P.B. Kang has served on advisory boards for Lupin Pharmaceuticals and Italfarmaco, consulted for Neurogene, contributed to educational programs at PeerVoice and the France Foundation, and received research funding from ML Bio Solutions and Sarepta Therapeutics. He has served in editorial roles for Wiley (as Associate Editor of Muscle & Nerve until December 2024) and for the American Academy of Neurology (as Editor of Neurology Genetics beginning January 2025). P. Marks is a full-time employee of the United States Government. K.D. Mathews receives research funding from the Paul D. Wellstone Muscular Dystrophy Cooperative Research Center grant (NIH U54 NS053672) and the Centers for Disease Control (U01 DD001248). She serves as an advisory board member for the Muscular Dystrophy Association and the FSH Society; is a board member for the Friedreich Ataxia Research Alliance; has served on advisory boards for Sarepta, Dyne, Edgewise, Ikaika, ML Bio Solutions, AskBio; and receives or has recently received clinical trial funding from PTC Therapeutics, Sarepta Therapeutics, Capricor, Edgewise, Lexeo, Pfizer, Reata, Italfarmaco, Fibrogen, ML Bio Solutions, AskBio, Biohaven, Scholar Rock, and AMO. J.R. Mendell currently serves as a Senior Advisor to Sarepta Therapeutics and is co-inventor of SRP-9003. L. Rodino-Klapac is an employee of Sarepta Therapeutics and may own stock/options in the company. She is a co-inventor of SRP-9003. D. Sproule is an employee of ML Bio Solutions and may own stock/options in the company. N. Verdun and K. Bryant have nothing to disclose. Full disclosure form information provided by the authors is available with the full text of this article at Neurology.org/cp.
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