BMECHE Resarch Seminar: Richard Price (UVA) - To the Blood-Brain Barrier and Beyond!

Richard Price, Ph.D. (RIT Mechanical Engineering BS Alum 1990)
Professor of Biomedical Engineering, University of Virginia

To the Blood-Brain Barrier and Beyond!
MRI-Guided Drug and Gene Delivery with Focused Ultrasound

Capillaries in the brain are highly-specialized. In addition to permitting oxygen and glucose transport from blood to brain tissue, they form a remarkably tight physical barrier [i.e. the blood-brain barrier (BBB)] that protects the brain from potentially harmful substances in the bloodstream. Ironically, this protective feature of the BBB also creates significant challenges for treating diseases of the brain, as systemically-administered drug and gene therapies are unable to cross the BBB to reach their target. In an effort to overcome this hurdle, our group investigates an MR image-guided approach for transiently opening the BBB to permit the targeted delivery of drugs and genes to the brain. This approach entails focusing pulsed ultrasonic energy to the site of treatment while microbubbles are circulating in the bloodstream. The microbubbles oscillate in the ultrasound field, exerting carefully tuned mechanical forces on the capillary walls that “loosen” the BBB, thereby permitting drug and gene delivery from the bloodstream to brain tissue.
In this talk, I will highlight several applications of this platform technology. Specifically, we have (i) delivered non-viral gene-bearing nanoparticles across the BBB in models of Parkinson’s disease to generate targeted expression of a potent neurotrophic factor (GDNF) and restore motor function, (ii) tuned focused ultrasound parameters to achieve endothelial cell-selective transfection of the cerebrovasculature, an approach with potential to prevent cerebral cavernous malformations, and (iii) delivered immuno- and chemo-therapies to infiltrative brain tumors to control tumor growth and improve survival. Notably, clinical trials are now underway at UVA wherein glioblastoma patients are being treated with this focused ultrasound approach to improve the chemotherapy delivery after surgical resection of the tumor.

In person INS 73-1180 and zoom: https://rit.zoom.us/j/96134371398