Therapeutics Core
Director:
Janice Clements, PhD
Professor of Comparative Medicine
Co-Directors:
M. Christine Zink, DVM, PhD
Professor of Comparative Medicine
Joseph Steiner, PhD
Assistant Professor of Neurology
Ahmet Hoke, MD
Associate Professor of Neurology and Neurosciences
Goals and Objectives
The Therapeutics Core was designed to accomplish the following goals and objectives:
- To use high throughput screening (HTS) assays to identify and characterize novel therapeutic compounds that can be specifically directed at treating HIV-associated CNS disease. *
- To generate and maintain pigtailed macaques that will be used for screening selected novel therapeutic compounds identified in Objective 1. **
* 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 (HTS) 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.
** Well-characterized animal models are essential for assessing the capacity of candidate compounds to protect against SIV/HIV-induced neurological disease. We have developed an SIV/macaque model in which the majority of macaques rapidly develop SIV CNS disease that recapitulates the characteristic pathological and behavioral features of HIV-associated CNS disease (24). This model has been successfully used to evaluate the effectiveness of a number of anti-HIV and neuroprotective therapeutics. Candidate drugs identified through this strategy are already entering clinical trials. This Core will support the purchase and maintenance of pigtailed macaques and will use macaques produced during the funding period to screen the novel therapeutic compounds identified in Objective 1. An algorithm of how the core services will be used to evaluate potential neuroprotective agents is given below:
