Quantitative magnetic resonance imaging measures as biomarkers of disease progression in boys with Duchenne muscular dystrophy: a phase 2 trial of domagrozumab.
Biomarkers
Domagrozumab
Duchenne muscular dystrophy
Imaging
MRI
Neuromuscular disease
Journal
Journal of neurology
ISSN: 1432-1459
Titre abrégé: J Neurol
Pays: Germany
ID NLM: 0423161
Informations de publication
Date de publication:
Aug 2022
Aug 2022
Historique:
received:
23
11
2021
accepted:
12
03
2022
revised:
11
03
2022
pubmed:
10
4
2022
medline:
22
7
2022
entrez:
9
4
2022
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 35396602
doi: 10.1007/s00415-022-11084-0
pii: 10.1007/s00415-022-11084-0
pmc: PMC9294028
doi:
Substances chimiques
Antibodies, Monoclonal, Humanized
0
Biomarkers
0
domagrozumab
516MD5WQ24
Banques de données
ClinicalTrials.gov
['NCT02310763']
Types de publication
Clinical Trial, Phase II
Journal Article
Multicenter Study
Randomized Controlled Trial
Langues
eng
Sous-ensembles de citation
IM
Pagination
4421-4435Subventions
Organisme : NCATS NIH HHS
ID : UL1 TR002538
Pays : United States
Informations de copyright
© 2022. The Author(s).
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