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Ready-Made Drugs May Halt AIDS-Related Infection

Generic antipsychotics block virus, finds study

THURSDAY, Nov. 18, 2004 (HealthDayNews) -- Generic medications used to treat other disorders may also be able to stop a fatal viral infection that's nearly untreatable right now and that's become increasingly common among AIDS patients.

Researchers from Brown University found some antipsychotic medications, and possibly even an antihistamine, can block a receptor, called 5HT2A, that lets a virus known as JCV enter the central nervous system. Once the virus gets into the nervous system, it progresses to the disorder called progressive multifocal leukoencephalopathy (PML), which causes dementia, vision loss, movement and speech impairment, and even death.

The virus is very common -- up to 80 percent of American adults carry it. Fortunately, PML is relatively rare, affecting only one in every 200,000 people. In people with AIDS, however, that number is much higher. Almost 4 percent of people with AIDS develop the disorder. People who have had transplants or cancer treatment or who have a compromised immune system for other reasons are also susceptible to the disorder. The incidence of PML has increased 50-fold since 1979, largely due to the rise in the number of people with AIDS, according to the study.

"These results open up the possibility that drugs that target the 5HT2A receptor might be useful in preventing the development of PML in AIDS patients given such drugs prophylactically, or they may prevent disease progression in patients already diagnosed with the disease," said study author Walter Atwood, an associate professor of medical science at Brown University in Rhode Island.

Atwood and his colleagues report their findings in the Nov. 19 issue of Science.

Because so many people carry the JCV virus yet so few develop PML, the researchers wanted to figure out how the virus was entering the cells in the central nervous system.

They tested the drug, chlorprozamine, which is normally used to control psychotic symptoms, and found that it was able to stop JCV from entering cells. But chlorprozamine has many troubling side effects, such as low blood pressure and tremors, so they searched for other drugs that might have the same effect.

After testing seven more medications, the researchers found three other drugs could prevent the virus from entering nervous system cells. The medications had one thing in common -- they all blocked the serotonin receptor 5HT2A.

That made Atwood and his colleagues wonder if they'd discovered how JCV gets into cells. They tested special cells that don't express 5HT2A and found those cells couldn't be infected by JCV. Then, they altered these cells to express the receptor, the JCV virus could enter the cells, proving that the 5HT2A receptor is the virus's way in.

"We wanted to know how the virus gets in, and they've found the door," said Dr. Charles Gonzalez, an infectious disease and immunology specialist at New York University Medical Center. "Not only did they find the door, but they figured out how to stop the virus from using the key to open the lock."

What's most exciting though, he said, is that the drugs that block the receptor have already been approved for use in other disorders by the U.S. Food and Drug Administration.

"For patients and doctors, this is a home run," said Gonzalez.

Atwood cautioned that his work was only done on cells in the lab; the drugs haven't been used to treat someone with PML yet.

However, he pointed out that the antihistamine cyproheptadine, which is sometimes prescribed as an appetite stimulant for people with AIDS, also blocks 5HT2A. Since this drug is relatively benign, he said doctors may start using it "off-label" to treat or try to prevent PML. Atwood is working with neurology centers to try to set up small-scale clinical trials to see if cyproheptadine can, in fact, prevent PML.

"Basic research sometimes unexpectedly gives you quick and simple results," said Gonzalez. "The fact that this won't take much is great in terms of prevention."

More information

To learn more about progressive multifocal leukoencephalopathy, visit the National Institute of Neurological Diseases and Stroke.

SOURCES: Walter Atwood, Ph.D., associate professor, medical science, Brown University, Providence, R.I.; Charles Gonzalez, M.D., infectious disease and immunology specialist, New York University Medical Center, and assistant professor, New York University School of Medicine, New York City; Nov. 19, 2004, Science
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