San Francisco Chronicle - October 15, 2004
Sabin Russell, srussell@sfchronicle.com

With prospects for an AIDS vaccine dimming, there is renewed -- and some would argue, overdue -- interest in chemicals, creams or gels that kill HIV or otherwise block its sexual transmission.

Unlike condoms, the use of these so-called microbicides could be controlled by women, who are being struck down in disproportionate numbers by AIDS in Africa and in poor nations throughout the world.

The latest finding involves a new strategy to block HIV infection, not by killing the virus but by shutting it out of the blood cells it normally attacks.

"It's very important for the field that this approach to preventing infection has been shown to work," said Zeda Rosenberg, chief executive of the Partnership for Microbicides, of Silver Spring, Md. Her group promotes and invests in research to speed development of microbicides.

The latest prospect is an experimental drug -- made by Gryphon Therapeutics of South San Francisco -- that blocks a critical doorway used by the AIDS virus to slip inside blood cells and cause them to churn out copies of itself.

In today's issue of the journal Science, an international team of researchers reports that high concentrations of the drug, known as PSC-RANTES, blocked infection in 13 out of 15 rhesus monkeys.

A teaspoon of a saline solution containing the drug was swabbed into the monkeys' vaginas shortly before they were dosed with a laboratory strain of SIV, which infects only monkeys.

At the highest concentrations of microbicide, five out of five of the animals were protected.

Dr. Michael Lederman, an AIDS researcher at Case Western Reserve University in Cleveland and lead author of the report, said the drug could be tested as a human microbicide in about a year, to determine if it is safe and that it does not inflame or sting sensitive tissues.

It is also critical to find a way to make it at a lower cost.

"Pennies per dose is what we need," Lederman said.

The experimental drug is currently made in small quantities, at great cost, but Gryphon Therapeutics has developed a technology that could be scaled up to bring down the price.

When the privately held company was formed in 1994, one of the co- founders was Robin Offord, a University of Geneva researcher who is co-author of the new study. According to Gryphon research and development director Gerd Kochendoerfer, the 60-employee company is using the same active ingredient in the microbicide as the basis for an experimental drug, Nonakine, to treat AIDS.

There are currently at least a dozen potential AIDS microbicides under study around the world. They include detergents and a derivative of seaweed that is currently used as a food additive. Many potential microbicides work on the concept of altering the acid balance in the vagina, making the environment hostile to HIV.

Initially, AIDS prevention experts had hoped that a common spermicide, nonoxynol-9, would also work as a microbicide. But the field endured a devastating setback in 2000, when a South African study of prostitutes found the spermicide actually increased HIV infection rates because it irritated tissues in the vaginal wall.

The Swiss and American study involves some of the most cutting-edge research in biology, where scientists have dissected molecular structures on the surface of blood cells and learned how proteins on the AIDS virus interact with them.

Lederman said the findings are significant because they suggest HIV infection might be blocked by targeting a single molecule found on the surface of blood cells -- the doorway protein known as CCR5. HIV normally grabs onto CCR5 and a companion protein, CD4, and muscles its way into the blood cell.

The new microbicide is based on a naturally occurring protein, RANTES, which is known to cause CCR5 to retract into the blood cell, shutting the door to HIV. With a few chemical tricks, Swiss researchers modified that protein into one that was 1,000 times more efficient, and dubbed it PSC-RANTES.

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