Title:New Developments of Clinical Trial in Immunotherapy for Alzheimer's Disease
Volume: 16
Issue: 6
Author(s): Cece Yang and Shifu Xiao
Affiliation:
Keywords:
Alzheimer’s disease, antibodies, clinical trials, immunotherapy, vaccines.
Abstract: Active or passive immunotherapy is expected to slow or stop the pathological process of
Alzheimer’s disease (AD). Immunotherapy for AD has demonstrated that targeting beta-amyloid (Aβ)
or tau protein with vaccines or antibodies can reduce AD pathologies. Active anti-Aβ immunization
for AD includes using AN1792 and second generation vaccines such as ACC-001, CAD106 and AFFITOPE
vaccines, while antibodies for passive immunization include monoclonal antibodies and intravenous
immunoglobulin (IVIG). Preclinical trials have shown powerful evidence of significant advances
for more than a decade; however, there are still issues that need to be addressed in clinical trials.
In the phase IIa AN1792 trial, 6% of patients who received the vaccination were diagnosed with meningoencephalitis
as an adverse effect. There was a high incidence of amyloid-related imaging abnormalities (ARIA) in patients treated with
some monoclonal antibodies. Moreover, several phase 3 clinical trial findings of immunization targeting Aβ were negative.
These issues require attention in order to improve the safety and efficacy of immunization strategies in AD. Prevention
studies and other novel immunization strategies have the potential to dramatically impact AD care. Herein we review
the recent advances in clinical trials involving immunotherapy for AD.