A $6 million, five-year federal grant to The Children's Hospital of Philadelphia Research Institute will enable researchers to investigate a novel approach in treating HIV infection---a unique class of drugs focused on developing therapies for psychological and neurological effects in AIDS.
Unlike many current HIV treatments, which are combinations of antiretroviral drugs, the compounds being studied cross into the brain, where HIV, the virus that causes AIDS, persists as a reservoir of infection, and causes dementia and cognitive impairments. In addition to studying the drug's direct antiviral activity, the researchers will investigate its potential benefits in relieving depression-like symptoms in HIV-infected patients. They will also study whether the drug improves innate immunity.
The National Institute of Mental Health (NIMH) has awarded a cooperative program grant, classified as a U01 grant, entitled, "Anti-HIV Neuroimmodulatory Therapy with Neurokinin-1 Antagonists," to a team led by principal investigator Steven D. Douglas, M.D., chief of the Section of Immunology and director of Clinical Immunology Laboratories at The Children's Hospital of Philadelphia.
As program director, Douglas oversees projects within the grant led by collaborators from Children's Hospital, the University of Pennsylvania School of Medicine, and the contract research organization Westat. This grant began Aug. 1, 2009.
At the heart of the program are drugs that target the neurokinin-1 receptor (NK1R) in human immune cells. Douglas and colleagues discovered in 1997 that human immune cells bear those cell receptors, and also produce substance P, a well-known neurotransmitter that binds to NK1R. In 2001, he showed in cell studies that an NK1R antagonista compound that binds to the NK1R receptor in immune cellsinhibits HIV from entering those cells by down-regulating, or dialing down the activity, of CCR5, a major HIV co-receptor on cell surfaces.<
|Contact: John Ascenzi|
Children's Hospital of Philadelphia