Development of Novel Therapeutic Agents for HIV Dementia

The dentate gyrus of a transgenic animal in which the HIV envelop protein, gp120, is expressed in astrocytes. In this figure, the neurons stain blue, astrocytes are green and the gp120 is red.

The goal of this project is to use high throughput screening assays to identify and characterize novel therapeutic compounds that can be specifically directed at treating HIV-associated CNS disease. Current antiviral therapies for HIV pose a number of challenges including the high cost of treatment, poor drug penetration into the CNS, development of resistant mutations, sometimes complicated dosing regimens and significant neurotoxicity. The major objective of this core is to use high throughput screening assays to identify novel therapeutic compounds that can be specifically directed at treating HIV-associated CNS disease. After validation of the efficacy and determination of potency in in vitro tests, the physicochemical properties and pharmaceutical characterization of the new lead compounds will be completed. Oral bioavailability, safety toxicology and CNS penetration of these potential therapeutics will be determined in rats and the most promising of these drugs will then be examined the SIV/macaque model for antiretroviral and neuroprotective properties or in human clinical trials.