Drug delivery through the opened blood-brain barrier in mice and non-human primates

Abstract

Over five million U.S. men and women suffer from neurodegenerative diseases. Although great progress has been made in recent years toward understanding of these diseases, few effective treatments and no cures are currently available. This is mainly due to the impermeability of the blood-brain barrier (BBB) that allows only 5% of more than 7000 small-molecule drugs available to treat only a tiny fraction of these diseases. Safe and localized opening of the BBB has been proven to present a significant challenge. Focused ultrasound (FUS), in conjunction with microbubbles, remains the sole technique that can induce localized BBB opening noninvasively and regionally. In the past, our group has focused on cavitation monitoring during BBB opening in both mice and non-human primates, assessment of safety and drug efficacy using behavioral testing, delivery of molecules of variant size through the opened BBB, investigation on the role of the microbubble diameter and use of nanodroplets. We will briefly highlight these past findings as well as introduce newer accomplishments such as its role in enhancement of drugs for neuroprotection and neuroregeneration in the treatment of Parkinson's, the use of alternative routes of systemic administration for larger drug dosage, dependence of the BBB opening size on the acoustic pressure, real-time monitoring of the microbubble perfusion of the brain, cavitation prediction of the timeline of BBB opening, and targeted delivery using adeno-associated viruses.