Amyloid-based immunotherapy for Alzheimer's disease in the time of prevention trials: the way forward.
Both active and passive anti-β-amyloid (Aβ) immunotherapies for the treatment of Alzheimer's disease (AD) have demonstrated clearance of brain Aβ deposits. Among passive immunotherapeutics, two Phase III clinical trials in mild-to-moderate AD patients with bapineuzumab, a humanized monoclonal antibody directed at the N-terminal sequence of Aβ, were disappointing. Also solanezumab, directed at the mid-region of Aβ, failed in two Phase III trials in mild-to-moderate AD. Another Phase III trial with solanezumab is ongoing in mildly affected AD patients based on encouraging results in this subgroup. Second-generation active Aβ vaccines (CAD106, ACC-001, and Affitope AD02) and new passive anti-Aβ immunotherapies (gantenerumab and crenezumab) have been developed and are under clinical testing. These new anti-Aβ immunotherapies are being tested in prodromal AD, in presymptomatic subjects with AD-related mutations, or in asymptomatic subjects at risk of developing AD. These primary and secondary prevention trials will definitely test the Aβ cascade hypothesis of AD.
Department of Basic Medicine, Neuroscience, and Sense Organs, Neurodegenerative Disease Unit, University of Bari Aldo Moro, Bari, Italy.
Francesco
F
Panza
Vincenzo
V
Solfrizzi
Bruno P
BP
Imbimbo
Rosanna
R
Tortelli
Andrea
A
Santamato
Giancarlo
G
Logroscino
D000544:Alzheimer Disease / Q000276:immunology / Q000628:therapy*; D000682:Amyloid / Q000037:antagonists & inhibitors / Q000276:immunology; D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use*; D002986:Clinical Trials as Topic; D006801:Humans; D007167:Immunotherapy / Q000379:methods* / Q000639:trends; D014612:Vaccines
D000682:Amyloid; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D014612:Vaccines; C571128:gantenerumab; C550616:solanezumab; C545458:bapineuzumab; C573372:crenezumab