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Amyotrophic lateral sclerosis is a pernicious neurodegenerative disorder that is associated with the progressive degeneration of motor neurons, the disruption of impulse transmission from motor neurons to muscle cells, and the development of mobility impairments. Clinically, muscle paralysis can spread to other parts of the body. Hence it may have adverse effects on swallowing, speaking, and even breathing, which serves as major problems facing these patients. According to the available evidence, no definite treatment has been found for amyotrophic lateral sclerosis (ALS) that results in a significant outcome, although some pharmacological and non-pharmacological treatments are currently applied that are accompanied by some positive effects. In other words, available therapies are only used to relieve symptoms without any significant treatment effects that highlight the importance of seeking more novel therapies. Unfortunately, the process of discovering new drugs with high therapeutic potential for ALS treatment is fraught with challenges. The lack of a broad view of the disease process from early to late-stage and insufficiency of preclinical studies for providing validated results prior to conducting clinical trials are other reasons for the ALS drug discovery failure. However, increasing the combined application of different fields of regenerative medicine, especially tissue engineering and stem cell therapy can be considered as a step forward to develop more novel technologies. For instance, organ on a chip is one of these technologies that can provide a platform to promote a comprehensive understanding of neuromuscular junction biology and screen candidate drugs for ALS in combination with pluripotent stem cells (PSCs). The structure of this technology is based on the use of essential components such as iPSC- derived motor neurons and iPSC-derived skeletal muscle cells on a single miniaturized chip for ALS modeling. Accordingly, an organ on a chip not only can mimic ALS complexities but also can be considered as a more cost-effective and time-saving disease modeling platform in comparison with others. Hence, it can be concluded that lab on a chip can make a major contribution as a biomimetic micro-physiological system in the treatment of neurodegenerative disorders such as ALS.

Organ on a Chip: A Novel in vitro Biomimetic Strategy in Amyotrophic Lateral Sclerosis (ALS) Modeling