UCLA

Duchenne muscular dystrophy (DMD) is a progressive X-linked genetic neuromuscular disorder that primarily affects males, is characterized by muscle atrophy, progressing proximally to distally, due to a lack of functional dystrophin protein, and currently has no cure. The focus of this work is gaining a biomechanical understanding of disease progression and compensatory strategies through quantitative gait analysis and musculoskeletal modeling. Gait deviations such as excessive trunk lean, excessive anterior pelvic tilt, reduced hip extensor moments, increased plantar flexion and plantar flexor moments have been observed for this population and are the result of progressive muscle weakness. Data obtained via quantitative gait analysis has the potential to be a sensitive outcome measure for clinical trials in young boys with DMD. This was explored by determining that joint moments about the hip were sensitive to improvement with a corticosteroid intervention in a group of young boys with DMD, as compared to a steroid-na?ve group. The mechanical hypothesis of disease progression was explored through musculoskeletal modeling by calculating eccentric and concentric work performed by individual muscles during gait. Muscles that performed more eccentric work were generally those with a greater degree of involvement. Muscles with more involvement decreased work with disease progression. And there was an increase in work from distal muscles as the work from proximal muscles decreased. This laid groundwork towards linking two biomarkers of disease progression: muscle function during gait and fatty tissue infiltration as measured by imaging methods. Finally, Induced Acceleration Analysis was used to assess the efficacy of typical compensatory strategies that develop in response to proximal muscle weakness. To maintain ambulation, muscles must provide support and propulsion for the center of mass. With disease progression, the ability of proximal muscle decreases and contributions from distal muscles must increase to compensate. This work is the first study that uses quantitative gait analysis as an outcome measure for an intervention, and is the first study to use musculoskeletal modeling to analyze the biomechanics of gait in this population.