Exercise in a Dish: Studying the Effects of Activity Based Treatments for Neuromuscular Disorders with Human Induced Pluripotent Stem Cells and Optogenetics

The goal of the current proposal is to harness the power of this newly developed iPSCbased model of neuromuscular disease to effectively and efficiently examine the effects of neural activity on survival of patient-derived MNs. There is a vast pre-clinical literature that suggests activity based therapies such as exercise, electrical stimulation and transcranial magnetic stimulation could be useful to promote neuroprotection and neuroplasticity in variety of clinical scenarios. However, for multiple reasons likely ranging from species specific differences between humans and animal models, to the barriers associated with running a well-power, multicenter randomized control trial, we have had limited success with generating high level clinical evidence to support activity-based interventions in neuromuscular disease (White et al. 2004, Cochrane Database Syst. Rev. 4, CD003904; Voet et al. 2013, Cochrane Database Syst. Rev. 7, CD003907). I firmly believe that high throughput screening of multiple activity protocols with human iPSC preclinical models should not only help teach us about MN biology, but more importantly help us to better direct the focus of future clinical trials of activity-based rehabilitation treatments.