Atwood and team achieve breakthrough in finding drug for fatal brain virus

by Wendy Y. Lawton

The JC virus is common. About 70 percent of adults harbor it. But in people with suppressed immune systems - cancer patients undergoing chemotherapy, AIDS patients, kidney transplant recipients - this typically benign bug can travel to the brain and cause a rare and deadly condition.

This nervous system disorder, called PML for progressive multifocal leukoencephalopathy, triggers dementia, vision loss, paralysis, coma. Many people die within four months of onset. Brown virologist Water Atwood (left) has studied the JC virus for 10 years and runs one of the few labs in the world that aims to understand how it infects brain cells.

"Most labs working on the JC virus study bits and pieces," Atwood said. "When I came to Brown, I wanted to focus on studying the biology of the virus as a whole."

Recently, Atwood, an associate professor of medical science, and his team found that a handful of antipsychotic drugs prevent brain cells from becoming infected with the JC virus. The drugs may prove to be an effective, ready-made therapy for PML prevention or treatment.

Their results, published in the Nov. 19 issue of Science, were picked up by The New York Times, the BBC and newspapers in places as far away as Iran.

So how did researchers know which drugs would work? Based on previous research, Atwood knew that the virus attached to the membrane of brain cells, which engulf it. They knew the drug chlorpromazine, a low-intensity antipsychotic, stopped this process in certain cells. The drug works by binding to receptors, signal-catching molecules on the cell surface, for the neurohormones dopamine and serotonin.

Atwood was convinced that the virus invaded brain cells through dopamine receptors. But Gwen Elphick, a research associate in his lab, thought the virus slipped inside cells through serotonin receptors. They began to test a panel of drugs - and Elphick's hunch was correct. Only the drugs that bound to serotonin receptors blocked infection.

"I was shocked," Atwood says. "We've probably looked at more than a dozen antibodies in the past 10 years. And there it was."

Atwood is working with several clinical neurology centers, including one at Washington University in St. Louis, to begin testing. "This is very promising," Atwood says. "These are generic drugs we can take off the shelf that may help a lot of people.