June 2, 2008
BIRMINGHAM, Ala. - UAB (University of Alabama at Birmingham) neurosurgeon James Markert, M.D., is heading a clinical trial treating malignant glioma, the type of brain tumor diagnosed in Sen. Ted Kennedy., with a common but usually harmless virus. The virus - respiratory enteric orphan virus, or reovirus - inhabits the lungs and intestines of humans. By adulthood, most humans have been exposed to it but demonstrate no illness or effects from the infection.
When the virus is introduced directly to malignant glioma cells however, it appears to be able to infect the malignant cell and then replicate, killing the cell.
"Healthy, non-cancerous cells in our bodies have the ability to prevent reovirus from replicating, so that even if we are infected with the virus we do not usually exhibit significant symptoms," said Markert, professor and director of the UAB division of neurosurgery and principal investigator of the trial. "But brain tumor cells do not have that protection, due to a mutation in their DNA. The reovirus replicates, destroying the tumor cell, and the replicated virus goes in search of new tumor cells to infect."
About half of the 15,000 brain tumors diagnosed in the Unites States each year are malignant glioma, the most severe form of brain tumor. Survival rates are very poor, with as few as 10 percent of patients living for two years.
Two catheters are placed in a tumor mass during a stereotactic brain surgery procedure. The reovirus is then infused through the catheters over the course of three days. MRI imaging will be used to determine whether the tumor mass shrinks over time, indicating that the virus is destroying tumor cells.
Markert said the trial will also examine whether the virus will be effective against glioma cells that have begun to spread away from the primary tumor. Glioma cells can break away from a tumor mass and migrate to other parts of the brain, traveling along nerve transmission lines called axons.
Markert said there is evidence that reovirus, when infused slowly over several days, may have the same ability to travel via nerve axons, allowing the virus to pursue and destroy glioma cells away from the tumor mass itself.
Markert is the co-director of the UAB Brain SPORE, a $13 million grant from the National Institutes of Health to develop new therapies to treat brain cancer.