Background: Aerobic cycle-training (AT) can counter secondary muscle disuse and induce cardiovascular and muscle adaptations that improve exercise capacity and endurance in various neuromuscular disorders. Its therapeutic potential in DMD is understudied, possibly related to concerns that exercise may enhance muscle deterioration and lack of knowledge regarding appropriate exercise prescription parameters. Previous studies reported potential benefits of AT in DMD; however, the cycling-exercise was entirely motor-assisted and did not impose sufficient muscle overload for optimal physiological adaptations.
Objective: To establish an appropriate AT paradigm for DMD, using heart rate (HR) to define exercise load thresholds that are safe for muscle whilst promoting adaptations.
Methods: We devised a home-based, remotely supervised, 6-month cycle-training paradigm using a custom-built ergometer and exercise prescription parameters (3 times/week, 15-30 minutes/session, at 50-60% HR reserve) typical for clinical populations. In order to maintain HR in the appropriate zone (and provide sufficient muscle overload), intensity was adjusted by the researchers using closed-loop adaptive admittance control of the ergometer motor. Intervention safety and efficacy were assessed using: serum CK, echocardiogram, cycling time-to-fatigue (TTF), peak watts and submaximal HR during cycle testing, total bone density through DEXA, and muscle mitochondrial function through phosphocreatine recovery-time (PCr-rt, 31P-MR spectroscopy).
Results: 3 ambulatory DMD boys (8+0.5 years on stable daily steroids and normal ejection fractions) completed the 6-month intervention with >85% compliance at their prescribed HR-training zone (145-165 bpm) with no adverse events. Total work per exercise bout was progressively increased (4,000+1000 to 13,000+2000 joules, p<0.05), with boys cycling 7-10 watts at study end. After training, each patient improved (with average % change) in cycling TTF (+22%), peak watts (+35%), submaximal HR (-16%), bone density (+5%) and serum CK (-40%). PCr-rt measured in 2 boys decreased (30%), suggesting improved mitochondrial function. Conclusion: This study provides 1) the first detailed cycling exercise prescription parameters for ambulatory boys with DMD that are safe and effective, and 2) novel evidence that muscle disuse may be countered and physiological adaptation (cardiopulmonary and muscle) to improve endurance is possible in boys with DMD.