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Lookup NU author(s): Professor Michela GuglieriORCiD
This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).
© 2022, The Author(s). Duchenne muscular dystrophy (DMD) is a progressive, neuromuscular disorder caused by mutations in the DMD 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 (n = 120 aged 6 to < 16 years). 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. Trial registration: ClinicalTrials.gov identifier, NCT02310763; registered December 2014.
Author(s): Sherlock SP, Palmer J, Wagner KR, Abdel-Hamid HZ, Bertini E, Tian C, Mah JK, Kostera-Pruszczyk A, Muntoni F, Guglieri M, Brandsema JF, Mercuri E, Butterfield RJ, McDonald CM, Charnas L, Marraffino S
Publication type: Article
Publication status: Published
Journal: Journal of Neurology
Year: 2022
Volume: 269
Pages: 4421-4435
Print publication date: 01/08/2022
Online publication date: 08/04/2022
Acceptance date: 12/03/2022
Date deposited: 21/04/2022
ISSN (print): 0340-5354
ISSN (electronic): 1432-1459
Publisher: Springer Nature
URL: https://doi.org/10.1007/s00415-022-11084-0
DOI: 10.1007/s00415-022-11084-0
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