A monoclonal antibody targeting amyloid β (Aβ) restores complement factor I bioactivity: Potential implications in age-related macular degeneration and Alzheimer's disease.

ABSTRACT: Activation of the alternative complement cascade has been implicated in the pathogenesis of age related macular degeneration (AMD) and Alzheimer's disease (AD). Amyloid β (Aβ), a component of drusen, may promote complement activation by inhibiting CFI bioactivity. We determined whether Aβ reduced CFI bioactivity and whether antibodies against Aβ including a monoclonal antibody, GSK933776 could restore CFI bioactivity. We also measured CFI bioactivity in plasma of subjects with AMD and AD. In support of the GSK933776 development program in AMD (geographic atrophy), we developed a quantitative assay to measure CFI bioactivity based on its ability to cleave C3b to iC3b, and repeated it in presence or absence of Aβ and anti-Aβ antibodies. Using this assay, we measured CFI bioactivity in plasma

SUBMITTER: Lashkari K 

PROVIDER: S-EPMC5962057 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature