Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease affecting motor neurons and other neuronal cells, leading to severe disability and eventually death from ventilatory failure. It has a prevalence of 5 in 100,000, with an incidence of 1.7 per 100,000, reflecting short average survival. The pathogenesis is incompletely understood, but defects of RNA processing and protein clearance may be fundamental. Repeat expansions in the chromosome 9 open reading frame 72 gene (C9orf72) are the most common known genetic cause of ALS and are seen in approximately 40% of patients with a family history and approximately 10% of those without. No environmental risk factors are proved to be causative, but many have been proposed, including military service. The diagnosis of ALS rests on a history of painless progressive weakness coupled with examination findings of upper and lower motor dysfunction. No diagnostic test is yet available, but electromyography and genetic tests can support the diagnosis. Care for patients is best provided by a multidisciplinary team, and most interventions are directed at managing symptoms. Two medications with modest benefits have Food and Drug Administration approval for the treatment of ALS: riluzole, a glutamate receptor antagonist, and, new in 2017, edaravone, a free radical scavenger. Many other encouraging treatment strategies are being explored in clinical trials for ALS; herein we review stem cell and antisense oligonucleotide gene therapies.
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