A Rationally Designed Humanized Antibody Selective for Amyloid Beta Oligomers in Alzheimer's Disease.

ABSTRACT: Advances in the understanding of Alzheimer's disease (AD) suggest that pathogenesis is not directly related to plaque burden, but rather to soluble toxic amyloid-beta oligomers (AßO). Therapeutic antibodies targeting Aß monomers and/or plaque have shown limited efficacy and dose-limiting adverse events in clinical trials. These findings suggest that antibodies capable of selectively neutralizing toxic AßO may achieve improved efficacy and safety. To this end, we generated monoclonal antibodies against a conformational Aß epitope predicted by computational modeling to be presented on toxic AßO but not monomers or fibrils. The resulting lead antibody, PMN310, showed the desired AßO-selective binding profile. In vitro, PMN310 inhibited AßO propagation and toxicity. In vivo, PMN310 prevented A

SUBMITTER: Gibbs E 

PROVIDER: S-EPMC6614461 | biostudies-literature | 2019 Jul

REPOSITORIES: biostudies-literature