Assessment of rAAVrh.74.MHCK7.micro-dystrophin Gene Therapy Using Magnetic Resonance Imaging in Children With Duchenne Muscular Dystrophy

Abstract

Microdystrophin gene transfer using recombinant adeno-associated virus serotype rh74 (rAAVrh74) driven by a skeletal and cardiac muscle-specific promoter with enhanced cardiac expression (MHCK7) (SRP-9001) showed promise in an open-label gene transfer study in Duchenne muscular dystrophy (DMD), with robust transgene expression on muscle biopsy (74%-96% of fibers).¹ However, biopsy data reflect a small sample of muscle, whereas muscle quality in large muscle groups can be objectively and noninvasively measured using quantitative magnetic resonance imaging (qMRI) and spectroscopy (qMRS). qMRI and qMRS are powerful tools for monitoring disease progression and therapeutic response in DMD, and they correlate with and identify future loss of ambulatory function.^2-5 We hypothesized that qMRI and qMRS data (muscle fat fraction and bulk MRI transverse relaxation time [qT₂]) would be reduced in 3 boys treated with SRP-9001 compared with an age-matched natural history cohort treated with standard of care and a control group of individuals without DMD.