title: Amyotrophic Lateral Sclerosis, 2016: existing therapies and the ongoing search for neuroprotection.
abstract: BACKGROUND
  Amyotrophic lateral sclerosis (ALS), one in a family of age-related neurodegenerative disorders, is marked by predominantly cryptogenic causes, partially elucidated pathophysiology, and elusive treatments. The challenges of ALS are illustrated by two decades of negative drug trials.
  
  
  METHODS
  In this article, we lay out the current understanding of disease genesis and physiology in relation to drug development in ALS, stressing important accomplishments and gaps in knowledge. We briefly consider clinical ALS, the ongoing search for biomarkers, and the latest in trial design, highlighting major recent and ongoing clinical trials; and we discuss, in a concluding section on future directions, the prion-protein hypothesis of neurodegeneration and what steps can be taken to end the drought that has characterized drug discovery in ALS.
  
  
  CONCLUSIONS
  Age-related neurodegenerative disorders are fast becoming major public health problems for the world's aging populations. Several agents offer promise in the near-term, but drug development is hampered by an interrelated cycle of obstacles surrounding etiological, physiological, and biomarkers discovery. It is time for the type of government-funded, public-supported offensive on neurodegenerative disease that has been effective in other fields.
authors.affiliation: a Inserm U930, Equipe "neurogénétique et neurométabolomique" , Tours , France.|b Université François-Rabelais, Faculté de Médecine , Tours , France.|c Laboratoire de Biochimie et Biologie Moléculaire , CHRU de Tours , Tours , France.
authors.forename: H
authors.initials: H
authors.lastname: Blasco
authors.affiliation: a Inserm U930, Equipe "neurogénétique et neurométabolomique" , Tours , France.|b Université François-Rabelais, Faculté de Médecine , Tours , France.|c Laboratoire de Biochimie et Biologie Moléculaire , CHRU de Tours , Tours , France.
authors.forename: F
authors.initials: F
authors.lastname: Patin
authors.affiliation: a Inserm U930, Equipe "neurogénétique et neurométabolomique" , Tours , France.|b Université François-Rabelais, Faculté de Médecine , Tours , France.|c Laboratoire de Biochimie et Biologie Moléculaire , CHRU de Tours , Tours , France.
authors.forename: C R
authors.initials: CR
authors.lastname: Andres
authors.affiliation: a Inserm U930, Equipe "neurogénétique et neurométabolomique" , Tours , France.|b Université François-Rabelais, Faculté de Médecine , Tours , France.|d Centre SLA, Service de Neurologie , CHRU Bretonneau , Tours , France.
authors.forename: P
authors.initials: P
authors.lastname: Corcia
authors.affiliation: e Northern Navajo Medical Center , Neurology Unit , Shiprock , NM , USA.
authors.forename: P H
authors.initials: PH
authors.lastname: Gordon
mesh_terms: D000690:Amyotrophic Lateral Sclerosis / Q000175:diagnosis / Q000188:drug therapy* / Q000235:genetics; D015415:Biomarkers / Q000378:metabolism; D002986:Clinical Trials as Topic; D057180:Frontotemporal Dementia / Q000175:diagnosis / Q000188:drug therapy / Q000235:genetics; D006801:Humans; D006898:Hydroxylamines / Q000627:therapeutic use; D008559:Memantine / Q000627:therapeutic use; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D019782:Riluzole / Q000627:therapeutic use; D013482:Superoxide Dismutase / Q000235:genetics / Q000378:metabolism; D014805:Vitamin B 12 / Q000031:analogs & derivatives / Q000627:therapeutic use
chemical_list: D015415:Biomarkers; D006898:Hydroxylamines; D018696:Neuroprotective Agents; D019782:Riluzole; C019476:mecobalamin; D013482:Superoxide Dismutase; C486387:arimoclomol; D014805:Vitamin B 12; D008559:Memantine
keywords: Amyotrophic lateral sclerosis; biomarkers treatment; clinical trials; glutamate neurotoxicity; neurodegeneration; neuroprotection; pathophysiology