UAB (University of Alabama at Birmingham) researchers are investigating whether a common but usually harmless virus can be used to treat a particularly devastating type of brain tumor called malignant glioma. 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 James M. Markert, M.D., 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 17,000 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.
UAB is currently the only site participating in this Phase I/II trial sponsored by a Canadian biomedical company, Oncolytics Biotech Inc., using their proprietary formulation of human reovirus called REOLYSIN(R).
“The main purpose of the Phase I portion of the study is to determine whether the virus is safe.” said Markert. “Previous studies give us reason to believe it will be well-tolerated without negative side effects.”
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.
UAB plans to enroll 15 people with recurrent malignant glioma in the Phase I portion of the trial.