Characterization of patients with Becker muscular dystrophy by histology, magnetic resonance imaging, function, and strength assessments

Introduction/aims: Becker muscular dystrophy (BMD) is characterized by variable disease severity and progression, prompting the identification of biomarkers for clinical trials. We used data from an ongoing Phase II study to provide a comprehensive characterization of a cohort of patients with BMD, and to assess correlations between histological and magnetic resonance imaging (MRI) markers with muscle function and strength. Methods: Eligible patients were ambulatory males with BMD aged 18-65 years (200-450m on 6 minute walk test). The following were measured: function tests, strength, fat-fraction quantification using chemical shift-encoded MRI (whole thigh and quadriceps), and fibrosis and muscle fiber area (MFA) of the brachial biceps. Results: Of 70 patients screened, 51 entered the study. There was substantial heterogeneity between patients in muscle morphology (histology and MRI), with high fat replacement. Total fibrosis correlated significantly and mostly moderately with all functional endpoints, including both upper arm strength assessments (left and right elbow flexion Rho -0.574 and -0.588, respectively [both p<0.0001]), as did MRI fat fraction (whole thigh and quadriceps), e.g., with four stair climb velocity -0.554 and -0.550, respectively (both p<0.0001). Total fibrosis correlated significantly and moderately with both MRI fat fraction assessments (0.500 [p=0.0003] and 0.423 [0.0024], respectively). Discussion: In this BMD cohort, micro- and macroscopic morphological muscle parameters correlated moderately with each other and with functional parameters, potentially supporting the use of MRI fat fraction and histology as surrogate outcome measures in patients with BMD, although additional research is required to validate this. This article is protected by copyright. All rights reserved.