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OyaGen blazing path toward
anti-AIDS drug

UR team confirms discovery of body's natural defense

Nishad Majmudar
Staff writer, Rochester Democrat and Chronicle
September 1, 2005

Local researchers have confirmed the existence of an innate defense system in the body that explains why some people infected with the human immunodeficiency virus, or HIV, can keep the virus from progressing to its more fatal stages.

Dr. Harold Smith of the University of Rochester Medical Center said the research, which he conducted with fellow URMC scientist Dr. Xia Jin, brings the biotech company he founded one step closer to developing a therapeutic drug for HIV patients.

Such a drug, developed by UR spinoff company OyaGen Inc., would undergo preclinical trials to determine the dosage size, possible toxic effects and safety before clinical trials next year, Smith said. OyaGen recently raised $1.5 million in financing and is looking to raise another $10 million to $30 million for its upcoming trials and drug approval submission to the Food and Drug Administration next year, he said.

In their research, Smith and Jin confirmed a 2002 discovery made by scientist Dr. Michael Malim that identified A3G, an "editing enzyme" in the body's white blood cells, as one of the body's main defenses against HIV, which can progress into AIDS.

Following Malim's discovery, scientists began to believe that A3G could improve chances of survival for people with HIV, Smith said.

"We speculated that, if this is true, one should be able to look across the population and see" that HIV patients with higher resistance to the virus should have greater levels of A3G, he said.

Smith and Jin looked at the levels of A3G in six people not infected with HIV and 25 people who were HIV-positive. Of those 25 with HIV, 17 had normal disease progression and eight were "long-term non-progressors," or had not seen their HIV progress into AIDS despite having the virus for a long time. People with higher levels of A3G in the blood had lower levels of HIV progression.

The finding sheds light on how the body's natural anti-HIV defense works and also how scientists may be able to formulate a potential HIV treatment.

When HIV infects the body's cells, it codes a protein called Vif, the viral infectivity factor. Researchers say Vif attacks A3G and tricks the body into destroying it, allowing the HIV to replicate its genes and spread.

When enough A3G is present in white blood cells, however, A3G causes HIV to mutate each time it replicates until the virus essentially loses its genetic identity and can't reproduce.

OyaGen's drug would protect A3G, Smith said. And unlike other HIV drugs, which are foreign to the body, OyaGen's drug would take advantage of the body's innate defense system.

"Vif is like a pair of pliers that have to form a grip," Smith said. "What the drug does is knock the grip apart and allow A3G to survive."

Dr. Ann Sheehy, one of the scientists who made the initial A3G discovery with Malim, said the findings by Smith and Jin are "tantalizing."

"It's very exciting," said Sheehy, an assistant professor of biology at College of the Holy Cross in Worcester, Mass. "I e-mailed this off to Dr. Malim and we both think it's incredibly tantalizing. What an exciting thing to find. It gives you a whole area to go after as far as therapies go."

Smith said research into the human body's 14 editing enzymes, including A3G, might lead to drugs for a variety of disorders, including hepatitis B. For now, OyaGen is focusing on drugs to boost the body's defense against HIV.

OyaGen formed in 2003 through the University Technology Seed Fund, a fund managed by the Trillium Group, a Pittsford venture capital firm.

The company also has top scientists in the study of HIV under its wing. OyaGen has Malim, an infectious disease professor at King's College London, and Dr. Hui Zhang, associate professor of medicine at Thomas Jefferson University in Philadelphia, as scientific advisers.

"This is really the first time to show that the expression of A3G prevents HIV progression in a patient," Zhang said. "This is surprising."

Reprinted courtesy of the Democrat and Chronicle