Abstract
BACKGROUND AND OBJECTIVES: Becker muscular dystrophy (BMD) is due to Duchenne muscular dystrophy gene variants allowing partial expression of dystrophin. A detailed description of disease trajectories in different genetic subgroups, and the identification of factors predicting progressive vs stable disease, are indispensable for designing and interpreting current and future clinical trials. METHODS: We recruited male participants with a molecularly confirmed diagnosis of BMD at our Institution, and followed them up with an observational longitudinal design with functional evaluations, including North Star Ambulatory Assessment (NSAA), 6-minute walk test, and timed function tests. RESULTS: We recruited 107 participants. Time-to-event analyses of age at loss of ambulation estimated that only 25% of individuals with BMD lose ambulation by age 60 years. Functional measures, over a follow-up of a mean ± SD of 6.4 ± 3.5 evaluations per participant, and a time of 6.1 ± 3.6 years, showed a poor performance in the common deletions del 45-47 and del 45-48, and preserved muscle function with del 48 and deletions ending on exon 51. In the overall cohort, all measures declined significantly over time, but this decrease was more evident in genetic groups with more marked weakness, and in participants with baseline values of NSAA of 32/34 or lower. DISCUSSION: These data refine genotype-phenotype correlations in BMD; quantify the decline in several practical and reliable motor outcome measures, which can be directly applied to power calculations for clinical trials; and point to useful inclusion/exclusion criteria for trials. Long-term outcomes will serve as a comparator for "real-world" efficacy data of upcoming therapeutics.