NIH grant to study brain-wasting PML

[rusty charly]

Edward M. Johnson, Ph.D., professor and chairman of microbiology and molecular cell biology at Eastern Virginia Medical School (EVMS), received a grant totaling more than $1.8 million over five years to study the molecular mechanics of a brain disease that kills four percent of AIDS patients worldwide.

Funded by the National Institute of Neurological Disorders and Stroke, Johnson's research focuses on the JC virus, discovered in 1971 and named for the initials of a patient who died of progressive multifocal leukoencephalopathy, or PML. A disease that afflicts patients with a weakened immune system, PML kills by, essentially, causing the brain's neurons to short-circuit. Aggressive and incurable, PML can kill a patient just a few months after the onset of symptoms. The brain-wasting disease can occur even in patients whose AIDS is kept in check by aggressive antiretroviral drugs.

The JC virus, the focus of Johnson's study, causes the brain to lose myelin, the sheath that insulates the passage of nerve signals. Such demyelination is also found in diseases such as multiple sclerosis.

Although researchers have known for years that the JC virus caused the brain-wasting PML, nobody has figured out exactly how. In fact, researchers don't understand how the JC virus, or even the AIDS virus, gets into the brain through a kind of microscopic cheesecloth that filters from the blood anything that can harm the brain. Johnson speculates that the viruses may infect cells that are able to squeeze through the protective blood-brain barrier. "This remains an important problem to solve," Johnson said.

Johnson's newest five-year grant will help him unravel the mystery of exactly how the JC virus does its damage. While many have theorized that damaged immune systems of AIDS patients leave them vulnerable to otherwise benign viruses, Johnson, going a step further, believes that proteins produced by the AIDS virus, HIV, may actually supercharge the JC virus. To do this the HIV proteins interact with proteins produced by cells in the brain.

This prompts a molecular cascade that kills brain cells called oligodendrocytes. These cells have long, sticky tendrils that wrap around and insulate wire-like nerve fibers that connect the brain's neurons. Without this insulation, myelin, the brain's neurons misfire and then atrophy, leaving dead tissue scattered through the brain.

Because brain tissues don't divide, Johnson must conduct his study using oligodendrocytes removed from patients suffering from malignant brain cancer. Ironically, the cancerous cells are taken from patients whose cancer kills by causing massive overproduction of the cells that are destroyed in patients with PML.

If Johnson can decipher the molecular mechanics, the research could help doctors find a way to disrupt the sequences of infection in both PML and AIDS and help stop these diseases.

"The interaction of HIV with other viruses is definitely a target for therapeutic agents," he said.