M. Bomma, D. J. Lott, S. C. Forbes, V. Del Toro, D. Maldonado-Puebla, M. Paul, R. Sullivan, A. Carvill, A. Foy, R. Shih, J. A. Coppola, C. Leon-Astudillo, G. A. Walter, M. Daniels, K. Stubbs, W. Dixon, H. L. Sweeney, T. Taivassalo
Background: Duchenne muscular dystrophy (DMD) results from absence of dystrophin, causing sarcolemmal instability, progressive muscle and mitochondrial dysfunction and reduced cardiorespiratory fitness and bone density. Exercise may target these multisystem abnormalities but remains underutilized due to historical safety concerns and lack of disease specific guidelines for optimal dosing. We conducted an exploratory trial using personalized exercise prescription to assess adherence, safety and preliminary efficacy in DMD. Methods: Six ambulatory boys underwent 6-months of home-based, remotely-supervised leg cycling and isometric strengthening using individualized frequency, intensity and time parameters. Cycling was set to 40-60% of heart rate and strengthening to 50% maximal voluntary contraction (MVC). Safety was assessed by creatine kinase (CK), muscle MRS T2, and adverse events. Primary outcomes were 6-month change in peak oxygen uptake (VO2) and submaximal-cycling HR; secondary outcomes included muscle fat fraction, cross-sectional area (CSA) and peak strength; exploratory outcomes included bone density, pulmonary function and quality-of-life. Peak VO2 and CSA were contextualized against untreated DMD controls. Results: All participants completed the intervention with high adherence (88.5%) and no adverse events. Cycling averaged 2-3 times/week at HR 148+8 bpm for 21.9+3.9 minutes; strengthening averaged 1.8+0.6 sessions/week at 50% MVC. CK and MRS T2 remained stable. Peak VO2 and submaximal-cycling HR improved, CSA increased relative to controls, and hamstring strength increased. Bone density, forced vital capacity and quality-of-life scores showed favorable trends. Discussion: Appropriately dosed exercise is feasible, safe and may produce multisystem physiological benefits in boys with DMD, supporting personalized, physiologically monitored training as a complementary therapeutic strategy.