Optogenetic Control of the Blood Brain Barrier for Drug Delivery
Overview
The blood–brain barrier (BBB) remains a significant impediment to drug development for central nervous system (CNS) disorders. Our novel method provides a way to regulate the permeability of the BBB, enabling delivery of therapeutics to the brain with high spatial and temporal precision. It can also be used to control vascular properties such as vascular tone, arterial diameter, and vascular growth.
Market Opportunity
Though the BBB is crucial for normal brain function, in medical practice it is an obstacle that prevents almost all beneficial drugs from entering the brain. One method being extensively studied at this time is localized ultrasound pulsing of intravenously injected micro-bubbles. This method has several drawbacks: it requires MRI to guide focusing of the ultrasound; the opening compromises the BBB for at least 3–5 hours; and multiple uses can cause local reactivity or damage. Thus, there is a need for a simple, noninvasive way to regulate vascular permeability, especially at the BBB, with high spatial and temporal precision for delivery of therapeutics.
Innovation and Meaningful Advantages
Our method uses optogenetics and light to regulate the permeability of the endothelial cells of the BBB. The endothelial cells are infected with recombinant viruses that enable the cells to express an optogenetic reagent, and the infected cells are then contacted with light. Light activation of the optogenetic reagent changes the permeability of the endothelial cells, opening or closing the BBB and increasing or decreasing delivery of therapeutics from the bloodstream to the brain. We have also shown that BBB permeability can be regulated by leveraging endogenous opsins, such as melanopsin, as the optogenetic reagent.
Our method can be used to treat and prevent brain diseases such as Alzheimer’s, glioma, and epilepsy; vascular disease caused by failure in proper vascular tone, such as stroke, aneurysm, hypertension, and cardiac disease; and disease caused by abnormal vascular growth, such as retinopathy, cerebrovascular epilepsy, and cancer. It can also be used to change the permeability of endothelial cells at the blood–air barrier in the lung, to treat diseases such as lung cancer.
Collaboration Opportunity
We are interested in exploring 1) startup opportunities with investors in the drug delivery space; 2) research collaborations with leading pharmaceutical companies to refine this drug delivery methodology; and 3) licensing opportunities with pharmaceutical or biotech companies.
Principal Investigator
Christopher Moore, PhD
Professor of Neuroscience
Associate Director of the Carney Institute of Brain Science
Brown University
Brown Tech ID #2135
christopher_moore@brown.edu
https://vivo.brown.edu/display/cm78
IP Information
2018-12-11 US10,149,986B2; Issued.
2017-06-27 US9,687,672B2; Issued.