Gene Therapy for Brain Tumors in Early Testing Phase

Preliminary testing of gene therapy for brain tumors is underway at Baylor College of Medicine and The Methodist Hospital.

It has taken more than two years of laboratory and animal testing to ready the therapy for human trials.

"In this early stage, we are trying to determine the therapy's safety and look for toxic effects," says Dr. Robert G. Grossman, chairman of neurosurgery at Baylor and chief of the neurosurgery service at Methodist.

The doctors hope the therapy can one day be used as an additional treatment for malignant brain tumors. It has been tested on patients with glioblastoma and astrocytoma tumors.

Most malignant brain tumors are fatal, and surgery and radiation may add only a few months to the patient's life.

"The gene therapy treatment involves taking a common virus called an adenovirus and altering it," Dr. Grossman says.

In the laboratory, scientists change the adenovirus by removing the gene for making the virus reproduce and replacing it with a gene that will make the enzyme, thymidine kinase. Removing the gene that makes the virus reproduce keeps the adenovirus from spreading in the body.

"The altered adenovirus is injected into the brain tumor's center," Dr. Grossman says. "We use CT scans and a frame attached to the head to determine the precise location for the injection."

Once in the tumor, the adenovirus makes thymidine kinase. When exposed to the drug ganciclovir, thymidine kinase causes the drug to become a toxin.

"The cells making thymidine kinase, which are only the brain tumor cells, destroy themselves when exposed to ganciclovir," he says.

Fifteen patients will participate in the first phase. After surgery, each patient receives several ganciclovir treatments.

"The next step will be to take the least toxic, most effective dosage level and distribute it more evenly throughout the tumor," Dr. Grossman says. "This will involve multiple injections into the tumor."

The study, a collaboration of Dr. Savio Woo, formerly of Baylor, and Dr. David Shine and Dr. Todd Trask of Baylor's department of neurosurgery, involves patients who have tried all other treatments and have had recurrent tumors.

Dr. Grossman hopes that, combined with surgery and radiation, the treatment will one day provide longer remission and a possible cure.

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©2006 Texas Medical Center

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