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NeuroAIDS is Target of Federal Grant to Children's Hospital
Date:10/15/2009

cells -- inhibits HIV from entering those cells by down-regulating, or dialing down the activity, of CCR5, a major HIV co-receptor on cell surfaces.

The current grant program will investigate the most effective ways to use NK1R antagonists to block HIV from replicating, with the aim of bringing those agents closer to use as clinical treatments. One project will use a specific NK-1R antagonist, the FDA-approved anti-nausea drug aprepitant, in a clinical trial in adult patients with HIV infection. It will be a Phase 1B trial, an early-stage test designed primarily to determine drug safety. It is also intended to test the concept that the drug may reduce virus levels in patients in whom highly active antiretroviral therapy (HAART) has failed.

"Our major goal is to establish proof-of-principle that this class of drug can reduce virus levels and otherwise benefit patients," said Douglas. "We envision NK-1R antagonists as a potential key element of a combination therapy for patients with HIV infection."

An estimated 50 percent of AIDS patients suffer some form of neuropsychiatric impairment, such as HIV-associated dementia, which is not well controlled by current antiretroviral drugs that have limited ability to cross the blood-brain barrier. Furthermore, while current drugs have improved patient survival, HIV continues to develop drug resistance, while neurocognitive deficits persist, compelling researchers to devise new antiviral therapies.

NK1R antagonists show promise as potential new treatments, but much remains to be learned about their biology and activity. Douglas' new grant encompasses cell studies, translational work to apply basic knowledge to treatments, and a clinical trial. The new grant builds on a previous four-year NIMH grant just concluding. That grant included an animal study that showed aprepitant was tolerated in rhesus macaque monkeys. The grant also supported a double-blind clinical trial of aprepitant i
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SOURCE The Children's Hospital of Philadelphia
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