Therapeutic Development in Amyotrophic Lateral Sclerosis

Abstract Purpose Amyotrophic lateral sclerosis (ALS) is the most common motor neuron disease in adults. It is almost invariably lethal within a few years after the onset of symptoms. No effective treatment is currently available beyond supportive care and riluzole, a putative glutamate release blocker linked to modestly prolonged survival. This review provides a general overview of preclinical and clinical advances during recent years and summarizes the literature regarding emerging therapeutic approaches, focusing on their molecular targets. Methods A systematic literature review of PubMed was performed, identifying key clinical trials involving molecular therapies for ALS. In addition, the ALS Therapy Development Institute website was carefully analyzed, and a selection of ALS clinical trials registered at ClinicalTrials.gov has been included. Findings In the last several years, strategies have been developed to understand both the genetic and molecular mechanisms of ALS. Several therapeutic targets have been actively pursued, including kinases, inflammation inhibitors, silencing of key genes, and modulation or replacement of specific cell populations. The majority of ongoing clinical trials are investigating the safety profiles and tolerability of pharmacologic, gene, and cellular therapies, and have begun to assess their effects on ALS progression. Implications Currently, no therapeutic effort seems to be efficient, but recent findings in ALS could help accelerate the discovery of an effective treatment for this disease.