Key Points
- Researchers sought to improve the way that focused ultrasound is used to open the blood-brain barrier (BBB) in preclinical studies.
- The group synthesized, compared, and analyzed two protein binders that weaken the BBB before applying ultrasound energy.
- Pretreatment incubation of tight junction proteins with clinically suitable binders may improve BBB opening and increase the therapeutic window.
To improve the way that focused ultrasound is used to open the blood-brain barrier (BBB) in laboratory studies, Jürgen Götz and his team at Queensland Brain Institute sought the use of cellular binders to weaken the contacts between the cells that form the BBB before applying the ultrasound energy.
In the BBB, claudins are integral membrane proteins that help seal the cleft between adjacent brain microvascular endothelial cells. With the goal of increasing permeability in the BBB cells, the research team synthesized, compared, and analyzed two claudin-5 binders that weaken the BBB. The testing included both single and combination treatments wherein the group measured transendothelial electrical resistance and cargo leakage and analyzed confocal images.
When incubated over an extended period, the binders’ influence on BBB opening depended on the amount of incubation time and the concentration of the binder. The group concluded that pretreatment incubation of tight junction proteins with clinically suitable binders may facilitate safer and more effective ultrasound-mediated BBB opening in cellular and animal systems. They also hypothesized that the technique may be translatable to humans. First author Liyu Chen suggests that this may be important for broadening the therapeutic window of focused ultrasound BBB opening for delivery of the next generation of drugs.