Zhimin Huang, PhD
In Vivo Protein Engineering for Prolonged Site-Specific Brain Therapeutics
Abstract
Many neuropsychiatric disorders arise from dysfunction in specific brain circuits and are often treated with small molecule drugs that lack spatial specificity, affecting both diseased and non-diseased regions, leading to adverse effects. To address this, we developed Regionally Activated Interstitial Drugs (RAID), a paradigm for site-specific pharmacotherapy. RAID uses focused ultrasound to deliver a protein enzyme to targeted brain regions, enabling the local conversion of a systemically administered prodrug into its active form. Unlike traditional therapies, RAID facilitates prolonged, localized drug action even with an intact blood-brain barrier. Preliminary data show successful enzyme delivery, spatially specific prodrug activation, and control of specific behaviors. This proposal aims to extend RAID’s potential by prolonging enzyme retention and validating its efficacy in an animal model of depression, offering a noninvasive, site-specific therapy with fewer side effects.
The Faculty Starter Grant in Drug Delivery empowers our efforts to advance noninvasive, site-specific brain therapeutics, bringing us closer to precision treatments that enhance efficacy and minimize side effects. I am grateful to the PhRMA Foundation.
