Navigation Links
NeuroAIDS is Target of Federal Grant to Children's Hospital

Novel HIV Drug to be Studied in Cell Cultures and in Patients

PHILADELPHIA, Oct. 15 /PRNewswire-USNewswire/ -- 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 antagonist -- a compound that binds to the NK1R receptor in immune 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 in human subjects, with results due to be reported late this year.

In the new grant, one project focuses on cellular mechanisms -- how NK-1R drugs function in human immune cells and brain cells. The project leader is John Wolfe, V.M.D., Ph.D., a Children's Hospital of Philadelphia Research Institute scientist and a Penn professor of Pathology and Medical Genetics with special expertise in genetic and cellular mechanisms in the brain.

A second project addresses immune mechanisms, investigating whether clinical depression makes a person's immune cells more vulnerable to HIV infection. The researchers will also study how aprepitant may have a dual effect, both preventing HIV from entering cells and restoring the immune function of natural killer cells. People with depression show lower levels of natural killer cells, and NK1R drugs may act against depressive behavior. Douglas leads this project, working with co-investigators Jordan Orange, M.D., Ph.D., of Children's Hospital, an expert in natural killer cells, and Dwight Evans, M.D., chair of Psychiatry at the Penn School of Medicine. Evans is internationally prominent for studying the connections between depression and immune function.

The third project is a Phase 1B clinical trial, to be led by Pablo Tebas, M.D., clinical research site principal investigator of the AIDS Clinical Trials Unit at the Hospital of the University of Pennsylvania. That unit participates in IMPAACT -- the International Maternal Pediatric Adolescent AIDS Clinical Trials Group, of which Douglas is the overall principal investigator for IMPAACT's Philadelphia Clinical Trials Unit.

The trial, to be conducted in HIV-infected adult patients already receiving antiretroviral medicines, will test the safety of aprepitant in those patients. A second clinical study will test aprepitant as an antiviral agent in combination with ritonavir, another anti-HIV drug, in patients failing HIV therapy. The interactions between both drugs may strengthen the effects of aprepitant without increasing its dosage. The trial will measure antiviral activity as well as changes in depressive behavior and anxiety among the subjects.

Although aprepitant has a central role in the study projects, it may not ultimately be the drug used in future HIV clinics. "Aprepitant is the only FDA-approved drug among NK1R antagonists, but we expect that ultimately another compound in the same class will become a new anti-AIDS drug," says Florin Tuluc, M.D., Ph.D., of Children's Hospital, an expert on cell signaling who is a collaborator in the program. "We believe a NK1R antagonist will have an important role as a novel medicine in treating neuroAIDS."

About The Children's Hospital of Philadelphia: The Children's Hospital of Philadelphia was founded in 1855 as the nation's first pediatric hospital. Through its long-standing commitment to providing exceptional patient care, training new generations of pediatric healthcare professionals and pioneering major research initiatives, Children's Hospital has fostered many discoveries that have benefited children worldwide. Its pediatric research program is among the largest in the country, ranking second in National Institutes of Health funding. In addition, its unique family-centered care and public service programs have brought the 430-bed hospital recognition as a leading advocate for children and adolescents. For more information, visit

    John Ascenzi
    (Phone): 267-426-6055

SOURCE The Children's Hospital of Philadelphia

SOURCE The Children's Hospital of Philadelphia
Copyright©2009 PR Newswire.
All rights reserved

Related medicine news :

1. A new molecular zip code, and a new drug target for Huntingtons disease
2. Investigational Agent Targeting Metabotropic Glutamate 2/3 Receptors Demonstrates Antipsychotic Activity in Humans, Study in Nature Medicine Finds
3. National Council of Negro Women (NCNW) Partners With Sherwin-Williams to Target Lead Risks in Neglected Housing
4. U.S. Health Initiative Targets Aging Hispanics
5. Global Health Project targets reducing AIDS among Indias adolescents
6. Study suggests brain tumors need treatment with multiple targeted drugs
7. GP targets on heart disease should be simpler and based more on treatment and prevention
8. T vs. B: Re-engineered human T cells effectively target and kill cancerous B cells
9. Chronic infection persists by targeting stromal cell network in lymphoid organs
10. Prime Access Creates Groundbreaking Ads Targeting Urban Teens for the White Houses National Youth Anti-Drug Media Campaign
11. International Law Enforcement Operation Targets Underground Manufacture of Anabolic Steroids
Post Your Comments:
(Date:10/13/2015)... ... October 13, 2015 , ... ... management services, today announced its partnership with WPC Healthcare , a provider ... systems and organizes the data into an aggregated data repository necessary to perform ...
(Date:10/13/2015)... ... October 13, 2015 , ... ... announced today their sponsorship of the Microsoft Dynamics AXUG, GPUG and NAVUG Summits ... GPUG Summit and NAVUG Summit are independent user conferences designed and led by ...
(Date:10/13/2015)... ... 13, 2015 , ... Relay (, a technology company that ... significant contract that will provide its award-winning private messaging solution to Independence Blue ... success of its Relay program, IBX Wire™, which now has over 550,000 members ...
(Date:10/13/2015)... ... ... A child without a healthy mouth is much more likely to have ... system, has joined with Global Dental Relief (GDR) to help bring dental ... purchased, SmileCareClub will donate one clinic visit to a child in Kenya. , “When ...
(Date:10/13/2015)... ... October 13, 2015 , ... ... targets the unique health needs of new moms. Postnatal Omega-3, which has ... ), utilizes Nordic Naturals’ exclusive, new, ultra-concentrated omega-3 oil. This breakthrough ...
Breaking Medicine News(10 mins):
(Date:10/13/2015)... Oct. 13, 2015  SeraCare Life Sciences, a leading ... that the company,s precision medicine business unit has launched ... materials for next-generation sequencing (NGS)-based tumor profiling assays.  The ... the same mixture of mutations in key oncogenes and ... AF20 mix , but is offered at five additional ...
(Date:10/13/2015)... 2015  Graduate students across the country, with ... will soon have the opportunity to learn about ... drug discovery and development process. Eli Lilly and ... 10 leaders from academic institutions to create an ... of Drug Development."  Lilly will formally unveil the ...
(Date:10/13/2015)... WASHINGTON , Oct. 13, 2015 /PRNewswire/ ... the first-ever direct-to-consumer laboratory home testing kit ... and digital technologies provide an unparalleled, detailed ... of breast milk—fats, proteins, carbs and key ... digital portal for personal health tracking.  In addition, ...
Breaking Medicine Technology: