MR biomarkers predict clinical function in Duchenne muscular dystrophy

Alison M. Barnard, DPT, PhD,* Rebecca J. Willcocks, PhD,* William T. Triplett, BS, Sean C. Forbes, PhD,
Michael J. Daniels, ScD, Saptarshi Chakraborty, PhD, Donovan J. Lott, PT, PhD, Claudia R. Senesac, PT, PhD, Erika L. Finanger, MD, PhD, Ann T. Harrington, DPT, PhD, Gihan Tennekoon, MBBS, Harneet Arora, PT, PhD, Dah-Jyuu Wang, PhD, H. Lee Sweeney, PhD, William D. Rooney, PhD, Glenn A. Walter, PhD, and Krista Vandenborne, PT, PhD



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.


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.


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.


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.


Other Resources