In addition to studying direct antiviral action, the researchers will also look for effects on behavior. Because NK-1R antagonists are known to have antidepressant properties, any evidence of reduced anxiety-related behavior in animals may suggest potential important benefits for human HIV patients as well.
The grant includes four separate projects. Projects 1 and 2, led by virologist Wen-Zhe Ho, M.D., of Children's Hospital, and Dr. Douglas, respectively, aim to better understand the underlying mechanisms behind anti-HIV activity of NK-1R antagonists. The basic science research will particularly examine how these agents affect HIV-infected immune cells and how they also might protect the brain. "We know that substance P plays an important role in both the immune system and the central nervous system," said Dr. Douglas, "and we are testing the hypothesis that interfering with substance P receptors may reduce neurological injury from HIV infection."
Project 3, led by Andrew A. Lackner, Ph.D., D.V.M., director of the Tulane National Primate Research Center, will test whether NK-1R antagonists are safe in animals infected with simian immunodeficiency virus (SIV), which is analogous to HIV. This study aims to provide proof of concept for human trials under Project 4.
Project 4, led by Pablo Tebas, M.D., of the Department of Medicine at the University of Pennsylvania Medical School, will be a phase 1 (safety) trial of the NK-1R antagonist aprepitant (trade name Emend) in adults with HIV infection. Aprepitant is currently used to control nausea caused by chemotherapy; this project will determine whether the antagonist may also attack HIV infection in pati
Source:Children's Hospital of Philadelphia