title: Amyotrophic lateral sclerosis: drug therapy from the bench to the bedside.
abstract: Amyotrophic lateral sclerosis (ALS) is an unrelenting progressive neurodegenerative disease causing progressive weakness, ultimately leading to death. Despite aggressive research, the pathways leading to neuronal death are incompletely understood. Riluzole is the only drug clinically proven to enhance survival of ALS patients, but its mechanism of action is not clearly understood. In this article, the proposed pathophysiology of ALS is reviewed including glutamate excitotoxicity, oxidative stress, mitochondrial dysfunction, autoimmune mechanisms, protein aggregation, SOD1 accumulation, and neuronal death. Based on these mechanisms, past major ALS drug studies will be reviewed as well as promising current ALS drug studies, focusing on the advancement of these studies from the bench to the patient's bedside.
authors.affiliation: Department of Neurology, University of Utah School of Medicine, Salt Lake City, Utah 84132, USA. summer.gibson@hsc.utah.edu
authors.forename: Summer Bell
authors.initials: SB
authors.lastname: Gibson
authors.forename: Mark B
authors.initials: MB
authors.lastname: Bromberg
mesh_terms: D000690:Amyotrophic Lateral Sclerosis / Q000188:drug therapy* / Q000473:pathology / Q000628:therapy; D000975:Antioxidants / Q000627:therapeutic use; D018691:Excitatory Amino Acid Antagonists / Q000627:therapeutic use; D015316:Genetic Therapy; D006801:Humans; D007093:Imidazoles / Q000627:therapeutic use; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D011719:Pyrazines / Q000627:therapeutic use; D033581:Stem Cell Transplantation; D013482:Superoxide Dismutase / Q000096:biosynthesis / Q000235:genetics; D000072105:Superoxide Dismutase-1
chemical_list: D000975:Antioxidants; C572767:CK-2017357; D018691:Excitatory Amino Acid Antagonists; D007093:Imidazoles; D007166:Immunosuppressive Agents; D011719:Pyrazines; C000606290:SOD1 protein, human; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1