Generic antipsychotic drugs can protect brain cells from a virus that causes a fatal nervous system disorder, according to research conducted at Brown University and Case Western Reserve University.
The disorder, called progressive multifocal leukoencephalopathy or PML, affects hundreds of Americans with suppressed immune systems, including kidney transplant recipients, cancer patients undergoing chemotherapy and an estimated 4 percent of people with AIDS.
PML is caused by the JC virus, which destroys the cells that produce the fatty sheath that covers nerve cells. This causes dementia, vision loss, movement and speech impairment, paralysis and coma. The disorder is fast moving and fatal; Many patients die within four months after onset. PML is also on the rise. Due to the AIDS pandemic, incidence of the disorder rose 20-fold in the United States between 1979 and 1994, according to a study conducted by federal researchers.
But a team of scientists, led by Brown virologist Walter Atwood, has found that a handful of antipsychotic drugs can prevent brain cells from becoming infected by the JC virus. The drugs may prove to be an effective, ready-made therapy for PML prevention or treatment. Their results are published in the current issue of Science.
"This is very promising," Atwood said. "These are generic drugs we can take off the shelf that may help a lot of people."
"It is likely that there are many other drugs with none of the potential side effects of antipsychotic drugs that will also block infection," said co-author Bryan Roth, professor of biochemistry at the Case School of Medicine and director of the National Institute of Mental Health's Psychoactive Drug Screening Program.
Atwood, an associate professor of medical science in the Department of Molecular Microbiology and Immunology at Brown, has studied the JC virus for more than a decade. The virus is common – anywhere from 70 to 80 percent of adults carry it in a latent form – and it infects certain types of glial cells, which support and protect neurons. It travels to the brain in people with severely weakened immune systems. But scientists didn't know precisely how it infects those cells. Atwood knew that cellular entry depended on a particular protein, called clathrin, and began to test compounds that would block it.
Atwood tried chlorprozamine, a drug used to control psychotic symptoms such as hallucinations and delusions, and found that it worked. But chlorprozamine can cause serious side effects, such as lowered blood pressure, stiffness and tremors, so Atwood and his team tested seven similar drugs. They found that three others, most notably the antipsychotic clozapine, also prevented infection in human glial cells without troubling side effects.