September 29, 2021

Focus Ultrasound-Induced Blood-Brain Barrier Opening Enhances Anti-PGLU3 A-beta Antibody Delivery and Plaque Clearance

Praveen Bathini, PhD

 

Objectives: Blood-brain-barrier (BBB) presents a significant challenge for CNS drug delivery Transient opening of BBB using Focused Ultrasound (FUS) has been shown to enhance delivery of therapeutics to the brain. Here, we aimed to determine the effects of an anti-pyroglutamate-3 amyloid-beta mAb (07/2a) combined with FUS in an AD-like mouse model.

Methods: First, 24 mo-old APP/PS1dE9 mice were i.v. infused with a single dose of 300 μg 07/2a with or without hippocampal FUS sonication (n=5/group) and euthanized 4 or 72 hr later; brain antibody levels were measured by ELISA. Next, 16 mo-old APP/PS1dE9 mice were treated weekly for 3 weeks with PBS (n=9), 500 μg 07/2a alone (n=9), FUS alone (n=7) or 07/2a + FUS combination (n=6). Water T Maze (WTM) was performed 1-2 weeks later followed by euthanasia.

Results: FUS increased 07/2a mAb levels in brain by 5.9-fold 4 hr after treatment (mean=41.7 pg/mg mAb alone vs. 244 pg/mg mAb+FUS, p

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