title: Amyloid-directed monoclonal antibodies for the treatment of Alzheimer's disease: the point of no return?
abstract: BACKGROUND
  Two humanized monoclonal antibodies, bapineuzumab and solanezumab, directed against the N terminus and mid-region of β-amyloid (Aβ), respectively, were recently tested in large, long-term Phase III trials in patients with mild-to-moderate Alzheimer's disease (AD).
  
  
  METHODS
  This review discusses current clinical data on solanezumab, bapineuzumab and their failure in Phase III trials to show significant clinical benefits, as well as other monoclonal antibodies under investigation for AD.
  
  
  CONCLUSIONS
  Solanezumab showed some beneficial cognitive effects in mildly affected AD patients and this subgroup of AD patients is currently being tested in another Phase III trial to this subgroup of AD patients to confirm previous encouraging observations. Two other monoclonal antibodies, gantenerumab, which preferentially binds to fibrillar Aβ, and crenezumab, which preferentially binds to soluble, oligomeric and fibrillar Aβ deposits, are being tested in secondary prevention trials in presymptomatic subjects with autosomal dominant AD mutations. Solanezumab is also being tested in a prevention study in asymptomatic older subjects, who have positive positron emission tomography scans for brain amyloid deposits. These ongoing secondary prevention trials will tell us if Aβ really plays a crucial role in the pathophysiology of AD.
authors: University of Bari Aldo Moro, Department of Basic Medicine, Neuroscience, and Sense Organs, Neurodegenerative Disease Unit , Bari , Italy.
authors: Francesco
authors: F
authors: Panza
authors: Vincenzo
authors: V
authors: Solfrizzi
authors: Bruno P
authors: BP
authors: Imbimbo
authors: Giancarlo
authors: G
authors: Logroscino
mesh_terms: D000544:Alzheimer Disease / Q000188:drug therapy* / Q000276:immunology; D016229:Amyloid beta-Peptides / Q000276:immunology*; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use*; D006801:Humans; D016896:Treatment Outcome
chemical_list: D016229:Amyloid beta-Peptides; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; C571128:gantenerumab; C550616:solanezumab; C545458:bapineuzumab; C573372:crenezumab
keywords: Alzheimer’s disease; cognitive disorders; dementia; gantenerumab; monoclonal antibody; passive immunotherapy; prevention trials; solanezumab