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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.
Glossary
- BFLH=
- biceps femoris long head;
- DMD=
- Duchenne muscular dystrophy;
- FF=
- fat fraction;
- GRA=
- gracilis;
- MG=
- medial gastrocnemius;
- MR=
- magnetic resonance;
- MRS=
- MR spectroscopy;
- PER=
- peroneal group;
- qMR=
- quantitative MR;
- ROC=
- receiver operating characteristic;
- 6MWT=
- 6-minute walk test;
- SOL=
- soleus;
- STS=
- supine-to-stand;
- TA=
- tibialis anterior;
- TE=
- echo time;
- TP=
- tibialis posterior;
- TR=
- repetition time;
- VL=
- vastus lateralis
Footnotes
Go to Neurology.org/N for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article.
↵* These authors contributed equally to this work.
- Received March 12, 2019.
- Accepted in final form August 29, 2019.
- © 2020 American Academy of Neurology
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