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Potential new drugs plug brain's biological 'vacuum cleaner' and target HIV

In an advance toward eliminating pockets of infection in the brain that help make HIV disease incurable, scientists report the development of new substances that first plug the biological vacuum cleaner that prevents anti-HIV drugs from reaching the brain and then revert to an active drug to treat HIV. They describe the advance, which allows medications to cross the so-called "blood-brain barrier" (BBB) and treat brain diseases, in the Journal of the American Chemical Society.

Jean Chmielewski, Christine Hrycyna and colleagues explain that Human Immunodeficiency Virus infection remains incurable because HIV can sneak through the BBB -- a network of special blood vessels and cells that protects the brain from many harmful substances -- while many of the most powerful anti-viral medications cannot. A pump at the BBB suctions anti-viral medicines away like a biological vacuum cleaner, leaving a reservoir of HIV in the brain. To overcome this hurdle and get rid of the last footholds of HIV, the researchers set out to develop a new group of drugs that can plug up the vacuuming mechanism and then sneak across the BBB to fight HIV.

Their approach involves gluing two anti-HIV drug molecules together with a "tether." This dual drug plugs up the BBB vacuum cleaner and can then sneak across the BBB. Once across, the tether disintegrates, freeing the two drug molecules to kill the virus. "This overall strategy represents a platform technology that may be readily applied to other therapies with limited brain penetration," such as anticancer and anti-schizophrenia drugs, say the researchers.

Contact: Michael Bernstein
American Chemical Society

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