National Institutes of Health grants $6-million for brain disease research

Brown University, in collaboration with two other institutions, has been awarded a five-year, $6-million National Institutes of Health program project grant to help determine how a virus that can cause a rare brain disease attaches to host cells.

Progressive multifocal leukoencephalopathy (PML) occurs in patients with compromised immune systems, such as those who suffer from HIV and AIDS. It has increasingly occurred in some multiple sclerosis patients and others with autoimmune disorders who are being treated with drugs that suppress the immune system. It is almost always fatal.

Researchers hope that learning more about the mechanism of the virus that causes PML - the JC virus - will lead to treatments to combat or prevent the disease. The work, to be led by Walter Atwood, professor of medical science, will involve collaborations with research teams at Dartmouth College and the University of T-bingen in Germany.

"Each of the project leaders brings unique skills to bear on the problem. And as the work could not be done by any one of us individually, it represents a perfect collaborative opportunity," Atwood said.

Earlier research by Atwood and others has determined the cells to which the virus sticks and identified which receptors are involved. The process involves a complex of carbohydrate molecules with a protein in the central nervous system. One of the serotonin receptors in the carbohydrate complex serves to attach the virus to the cells.

The new grant will seek details about how the JC virus gains traction in the brain.

"The idea is to look at the surface of the virus now, and try to understand what parts of the virus interact with the receptors on the cell," said Atwood.

Scientists first isolated the JC virus in 1971 (JC stands for John Cunningham, a patient from whom the virus was first isolated). It is thought to be very common, with more than 70 percent of the human population already having been exposed to it.

The virus only causes disease in some immuno-suppressed patients, including a small number of patents with cancers such as non-Hodgkins lymphoma and some patients with AIDS.

In recent years, some antibody-based therapies for autoimmune diseases such as multiple sclerosis and Crohn's disease has left some patients vulnerable to PML.

The virus is considered challenging because there is no animal model of the virus, which makes it difficult to test the effectiveness of any therapy.