Widespread brain distribution and activity following i.c.v. infusion of anti-β-secretase (BACE1) in nonhuman primates.

ABSTRACT:

Background and purpose

The potential for therapeutic antibody treatment of neurological diseases is limited by poor penetration across the blood-brain barrier. I.c.v. delivery is a promising route to the brain; however, it is unclear how efficiently antibodies delivered i.c.v. penetrate the cerebrospinal spinal fluid (CSF)-brain barrier and distribute throughout the brain parenchyma.

Experimental approach

We evaluated the pharmacokinetics and pharmacodynamics of an inhibitory monoclonal antibody against β-secretase 1 (anti-BACE1) following continuous infusion into the left lateral ventricle of healthy adult cynomolgus monkeys.

Key results

Animals infused with anti-BACE1 i.c.v. showed a robust and sustained reduction (~70%) of CSF amyloid-β (Aβ) peptides. Antibody dist

SUBMITTER: Yadav DB 

PROVIDER: S-EPMC5659992 | biostudies-literature | 2017 Nov

REPOSITORIES: biostudies-literature