title: Therapeutic development in amyotrophic lateral sclerosis.
abstract: OBJECTIVE
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors: Dino Ferrari Centre, Department of Neurological Sciences, University of Milan, IRCCS Foundation Ca' Granda Maggiore Hospital Policlinico, Milan, Italy.
authors: Monica
authors: M
authors: Bucchia
authors: Dino Ferrari Centre, Department of Neurological Sciences, University of Milan, IRCCS Foundation Ca' Granda Maggiore Hospital Policlinico, Milan, Italy.
authors: Agnese
authors: A
authors: Ramirez
authors: Dino Ferrari Centre, Department of Neurological Sciences, University of Milan, IRCCS Foundation Ca' Granda Maggiore Hospital Policlinico, Milan, Italy.
authors: Valeria
authors: V
authors: Parente
authors: Dino Ferrari Centre, Department of Neurological Sciences, University of Milan, IRCCS Foundation Ca' Granda Maggiore Hospital Policlinico, Milan, Italy.
authors: Chiara
authors: C
authors: Simone
authors: Dino Ferrari Centre, Department of Neurological Sciences, University of Milan, IRCCS Foundation Ca' Granda Maggiore Hospital Policlinico, Milan, Italy.
authors: Monica
authors: M
authors: Nizzardo
authors: Dino Ferrari Centre, Department of Neurological Sciences, University of Milan, IRCCS Foundation Ca' Granda Maggiore Hospital Policlinico, Milan, Italy.
authors: Francesca
authors: F
authors: Magri
authors: Dino Ferrari Centre, Department of Neurological Sciences, University of Milan, IRCCS Foundation Ca' Granda Maggiore Hospital Policlinico, Milan, Italy.
authors: Sara
authors: S
authors: Dametti
authors: Dino Ferrari Centre, Department of Neurological Sciences, University of Milan, IRCCS Foundation Ca' Granda Maggiore Hospital Policlinico, Milan, Italy. Electronic address: stefania.corti@unimi.it.
authors: Stefania
authors: S
authors: Corti
mesh_terms: D000328:Adult; D000690:Amyotrophic Lateral Sclerosis / Q000503:physiopathology / Q000628:therapy*; D018450:Disease Progression; D006801:Humans; D019782:Riluzole / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D019782:Riluzole
keywords: amyotrophic lateral sclerosis; clinical trials; molecular targets; motor neuron disease; small molecules