Case Western Reserve University School of Medicine researchers have been awarded a $5 million dollar grant from the National Institutes of Health (NIH) to continue their ground-breaking research on the development of an HIV microbicide, a potentially revolutionary tool in stemming the global HIV epidemic.
The three-year NIH award allows Case Western Reserve to continue to lead an international research team's development of molecules which stop HIV from entering cells, thus preventing HIV infection. The funding supports three interlocking projects which will provide information critical to the development of microbicides in general and more specifically to microbicidal strategies utilizing the team's molecules. This five million dollar grant is the most recent of several NIH grants received by this research team, ensuring Case Western Reserve's central role in the development of HIV microbicides. The Cleveland-based team includes researchers from Rush University Medical Center and Northwestern University in Chicago; The Scripps Research Institute, La Jolla, California; the University of Geneva, Geneva, Switzerland; and the Tulane National Primate Research Center in Covington, Louisiana.
An HIV microbicide is a topical treatment in the form of a gel, foam, or cream that could decrease or prevent the sexual transmission of HIV. The search for one has become an international priority as the disease has continued to spread around the world. An HIV microbicide would be of particular help in preventing new infections in women, who account for 50 percent of the 33 million HIV-infected people worldwide. In Sub-Saharan Africa, the region most devastated by the AIDS epidemic, more than 60 percent of the HIV-infected population is female. Unlike condoms, which require active male participation, a microbicide could be used by women without the participation, or even knowledge, of their male sexual partners. With recent disappointing results from HIV vaccine trials, the development of an HIV microbicide has become even more urgent. There are no current effective HIV microbicides products available to the public.
"NIH support has been crucial to our success to date. This grant will provide the continued investment needed to reach the next milestone," said Michael Lederman, lead investigator on the project and principal investigator of the Case Western Reserve University/University Hospitals AIDS Clinical Trials Unit. "It allows us to move closer to the day when our laboratory developments will become a safe, affordable and effective method for people, particularly women, to protect themselves from HIV infection."
In 2004, the Case Western Reserve research team achieved a landmark breakthrough with their publication in Science of their development of PSC-RANTES. In this work, PSC-RANTES provided protected rhesus monkeys from vaginal challenge with SHIV, a retrovirus containing surface structures of HIV. PSC-RANTES proved that blockading CCR5, an HIV co-receptor, provided complete protection from infection. While effective, PSC-RANTES was expensive to produce, making its development into an HIV microbicide less promising, as it would be less affordable to women in developing countries.
Earlier this year, the research team announced they had overcome the affordability barrier of PSC-RANTES. "Based on our earlier research," Lederman said. "We have been able to develop two new molecules, 6P-4 RANTES and 5P-12 RANTES, which are equally as protective as PSC-RANTES in blocking HIV entry into cells and in protecting rhesus macaques from SHIV infection. Most importantly however, the new molecules can be developed for pennies per dose, which makes them affordable in the developing world where they are needed the most."
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