Antibody blood-brain barrier efflux is modulated by glycan modification.

ABSTRACT:

Background

Drug delivery to the brain is a major roadblock to treatment of Alzheimer's disease. Recent results of the PRIME study indicate that increasing brain penetration of antibody drugs improves Alzheimer's treatment outcomes. New approaches are needed to better accomplish this goal. Based on prior evidence, the hypothesis that glycan modification alters antibody blood-brain barrier permeability was tested here.

Methods

The blood-brain barrier permeability coefficient Pe of different glycosylated states of anti-amyloid IgG was measured using in vitro models of brain microvascular endothelial cells. Monoclonal antibodies 4G8, with sialic acid, and 6E10, lacking sialic acid, were studied. The amount of sialic acid was determined using quantitative and semi-quantitative su

SUBMITTER: Finke JM 

PROVIDER: S-EPMC5557653 | biostudies-literature | 2017 Sep

REPOSITORIES: biostudies-literature