Immunotherapy targeting Aβ for Alzheimer's disease

Abstract

Alzheimer's disease is characterized by deposition of aggregated amyloid β protein and tau protein. Since active and passive immunization of Alzheimer model mice with aggregated Aβ or antibody to Aβ showed clearance of aggregated amyloid β deposits and improved memory and learning, immunotherapy targeting Aβ is being developed. Although a human trial of active immunization with Aβ and adjuvant QS21 was halted because of autoimmune encephalitis, the trial revealed that it is possible to clear Aβ deposits in humans. On this proof of concept, several clinical trials using monoclonal antibodies are on–going. Although solanezumab which recognizes Aβ monomer turned out ineffective in the primary endpoint, it showed significant beneficial effect in mild AD cases in the secondary outcome. Therefore, solanezumab is now on a large scale phase III trial in mild AD cases in the world. If it turns out to be effective, it will be the first disease modifying drug for AD in a few years. However, since monoclonal antibodies are extremely expensive, less expensive and long acting active immunization with Aβ peptide (a vaccine) will be widely accepted, if it is safe. If peptide vaccines are successful, more effective and sophisticated vaccines such as safe DNA and recombinant viral vector vaccines will be utilized in future.