The development of therapeutics targeting Aβ oligomers

Abstract

Alzheimer's disease (AD) represents the so–called “conformational disorders”. From a therapeutic view point, identification of targeting molecules which can trigger a complex downstream cascade (e.g., primary amyloid–relating process or secondary tau–related neuronal degeneration process) leading to AD dementia is a promising strategy. Evidence has shown that amyloid β (Aβ), particularly Aβ oligomers (AβOs), plays a causative role in Alzheimer's disease. If AβO cascade hypothesis is valid, therapeutic intervention targeting AβOs or for preventing the interaction between AβOs and tau is a promising treatment strategy for AD. We performed a hypothesis–driven, proof of concept study to prove the relevance of the in vivo Aβ oligomer cascade hypothesis using novel monoclonal antibodies specific to AβOs.

We herein review our AβO–immunotherapy with particular focus in the confirmation the relevance of our therapeutic strategy, which resulted in the phase I trial in prodromal and early AD.