MR biomarkers predict clinical function in Duchenne muscular dystrophy
- 5 February 2020
- journal article
- research article
- Published by Ovid Technologies (Wolters Kluwer Health) in Neurology
- Vol. 94 (9), e897-e909
- https://doi.org/10.1212/wnl.0000000000009012
Abstract
Objective To investigate the potential of lower extremity magnetic resonance (MR) biomarkers to serve as endpoints in clinical trials of therapeutics for Duchenne muscular dystrophy (DMD) by characterizing the longitudinal progression of MR biomarkers over 48 months and assessing their relationship to changes in ambulatory clinical function. Methods One hundred sixty participants with DMD were enrolled in this longitudinal, natural history study and underwent MR data acquisition of the lower extremity muscles to determine muscle fat fraction (FF) and MRI T2 biomarkers of disease progression. In addition, 4 tests of ambulatory function were performed. Participants returned for follow-up data collection at 12, 24, 36, and 48 months. Results Longitudinal analysis of the MR biomarkers revealed that vastus lateralis FF, vastus lateralis MRI T2, and biceps femoris long head MRI T2 biomarkers were the fastest progressing biomarkers over time in this primarily ambulatory cohort. Biomarker values tended to demonstrate a nonlinear, sigmoidal trajectory over time. The lower extremity biomarkers predicted functional performance 12 and 24 months later, and the magnitude of change in an MR biomarker over time was related to the magnitude of change in function. Vastus lateralis FF, soleus FF, vastus lateralis MRI T2, and biceps femoris long head MRI T2 were the strongest predictors of future loss of function, including loss of ambulation. Conclusions This study supports the strong relationship between lower extremity MR biomarkers and measures of clinical function, as well as the ability of MR biomarkers, particularly those from proximal muscles, to predict future ambulatory function and important clinical milestones. ClinicalTrials.gov identifier NCT01484678.Keywords
This publication has 31 references indexed in Scilit:
- Skeletal Muscle Quantitative Nuclear Magnetic Resonance Imaging and Spectroscopy as an Outcome Measure for Clinical TrialsJournal of Neuromuscular Diseases, 2016
- Histologic muscular history in steroid-treated and untreated patients with Duchenne dystrophyNeurology, 2015
- Quantitative Skeletal Muscle MRI: Part 2, MR Spectroscopy and T2 Relaxation Time Mapping—Comparison Between Boys With Duchenne Muscular Dystrophy and Healthy BoysAmerican Journal of Roentgenology, 2015
- Quantitative muscle MRI: A powerful surrogate outcome measure in Duchenne muscular dystrophyNeuromuscular Disorders, 2015
- T2 mapping provides multiple approaches for the characterization of muscle involvement in neuromuscular diseases: a cross‐sectional study of lower leg muscles in 5–15‐year‐old boys with Duchenne muscular dystrophyNMR in Biomedicine, 2012
- Changes in muscle T2 and tissue damage after downhill running in mdx MiceMuscle & Nerve, 2011
- Surrogate Endpoints And FDA’s Accelerated Approval ProcessHealth Affairs, 2005
- Quantitative assessment of MRI T2 relaxation time of thigh muscles in juvenile dermatomyositisRheumatology, 2004
- Dystrophin protects the sarcolemma from stresses developed during muscle contraction.Proceedings of the National Academy of Sciences of the United States of America, 1993
- Dystrophin: The protein product of the duchenne muscular dystrophy locusCell, 1987