G.O.10

With the promise of new treatments for Duchenne muscular dystrophy (DMD), there is a need for development of noninvasive biomarkers to assess pharmacologic response to study drugs. Magnetic resonance imaging (MRI) is a valuable tool for measuring the changes in the fat and water signal characteristics in dystrophic muscle. We performed a prospective imaging study of skeletal, cardiac, and respiratory muscles as part of a phase 2, placebo-controlled study of oligonucleotide GSK2401968-induced exon skipping in ambulatory boys with DMD. Muscles in the legs from the hips to the ankles were imaged using T1w, T2w, and 3-point Dixon sequences. Cardiac MRI measures of left ventricle (LV) mass, volume, thickness, fat/water quantitation of the myocardium, LV strain, stroke volume, and ejection fraction were also obtained. In addition, we applied recent and exploratory MRI methods including IDEAL/CPMG, diffusion weighted MRI, and dynamic breathing MRI for muscle fat and water quantitation, sarcolemmal disruption, and the dynamics of diaphragm movement and lung volume changes across the respiratory cycle, respectively. The MRI measures were compared between boys with DMD at baseline ( n  = 13) and age range-matched healthy boys ( n  = 20). A subset of DMD subjects ( n  = 9) participated in the GSK2401968 study and had follow-up MRI studies at the 12, 24, and 48 weeks time points. All subjects underwent a standardized exercise of ankle dorsiflexion during each visit and had MRI of the lower leg muscles repeated after the exercise. The analysis of the imaging data is currently ongoing by blinded investigators and will be presented.