The investigation of amyotrophic lateral sclerosis (ALS) - also known as Lou Gehrig's disease - through muscle-on-a-chip technology has revealed a new drug combination that may serve as an effective treatment of the progressive neurodegenerative disease. These findings highlight organ-on-a-chip technologies - in which live conditions of the body are mimicked in a microfluidic cell culture - as promising platforms for testing drug candidates and investigating the pathogenesis of ALS, which remains largely unknown. The disease currently impacts around 12,000 to 15,000 people in the U.S. ALS involves the loss of motor neurons in the spinal cord and motor cortex, which leads to progressive paralysis, muscle atrophy and death. While roughly 10% of ALS patients have a familial version of the disease, which can typically be traced back to a genetic mutation, 90% of patients have "sporadic ALS," which has no known familial links or causes. As the few FDA-approved drugs currently on the market for ALS lack full effectiveness, there is an urgent need for ALS therapy investigations in the clinic, using better clinical models that can go beyond the limitations of animal models. Here, Tatsuya Osaki and colleagues created disease-on-a-chip technology-based approach. It features a microfluidic chip loaded with healthy skeletal muscle bundles and induced pluripotent stem cell-derived, light-sensitive motor neurons from a sporadic ALS patient. Light was used to activate muscle contraction and control neural activity on the chips. Compared to chips with non-ALS-patient-derived cells, the ALS-on-a-chip exhibited fewer and weaker muscle contractions, degraded motor neurons, and increased muscle cell death. Application of two neuroprotective molecules - rapamycin and bosutinib (both in clinical trials) - helped recover muscle contraction induced by motor neuron activity and improve neuronal survival in the chip-based model of disease. Importantly, each treatment on its own has a limited ability to penetrate the blood-brain barrier, but when combined, the molecular duo could efficiently cross blood-brain-barrier-like cell layers built onto the chip.