Gene therapy used for first time on brain tumor

The brain of a terminally ill cancer patient was injected with genetically engineered mouse cells Monday in the first experiment in treating brain tumors with gene therapy.

Neurosurgeons at the National Institutes of Health performed the treatment, which involves injecting foreign genes into tumor cells and then killing those cells with a drug, on a brain cancer patient who had not been helped by conventional treatments.


The operation was an important step for researchers who are seeking a gateway to cure a host of fatal diseases, from cystic fibrosis to cancer and AIDS, by tapping the basic building blocks of the human body.

"It is very significant not only for treating malignant brain tumors, but it [also] opens up the door to a whole new approach to treating tumors," said Dr. Henry Brem, director of neurosurgical oncology at the Johns Hopkins School of Medicine. "It is the first step to seeing the fulfillment of gene therapy."


The doctors said they will know within several weeks whether the treatment has shrunk the tumor in the patient, but it will be several months before they can tell whether the tumor will grow back.

Researchers also plan to treat two more patients within six weeks with the same method, and 20 patients in the near future.

If the method succeeds in many patients, doctors could ask the Food and Drug Administration next year for permission to use it more widely.

The experiment, conceived 20 months ago, has attracted the attention of cancer patients throughout the country, thousands of whom have telephoned the NIH, asking to be among the first patients to be treated. About 15,000 patients who are diagnosed with primary brain cancer each year typically face a poor prognosis.

This is not the first time that gene therapy has been used to treat patients. Researchers have asked the FDA for permission to conduct dozens of gene therapy experiments. But only a handful have begun.

Last week, a federal advisory committee, the Recombinant DNA Advisory Committee of the NIH, approved gene therapy treatment for cystic fibrosis, the most common inherited fatal disease. In October, the NIH granted researchers and GTI approval to treat lung cancer patients by inserting genes in their tumors.

Monday's experimental treatment was an important step in the furtherance of gene therapy, a potentially powerful treatment for all kinds of diseases.

In general, the process involves inserting a new gene into the human body. In some cases, the inserted gene is missing from the person's genetic makeup. By adding it to the body, researchers hope the gene can correct that deficiency and that the body cures itself. In other cases, such as cancer, researchers insert a foreign gene as a mechanism to aid the destruction of the tumor.


Two neurosurgeons, Dr. Edward Oldfield and Dr. Zvi Ram, inserted a needle into the tumor and injected millions of mouse cells.

These cells act like a small factory within the brain, churning out retroviruses that contain the herpes gene.

The mouse cells, engineered by a Gaithersburg company, Genetic Therapy Inc., have been modified to produce retroviruses that do not contain any infectious material, but which are an effective means of getting a gene into a cell.

The retroviruses are intended to insert themselves into the tumor cells as they replicate. Normal brain cells do not replicate and so should not be affected by the retroviruses.

About a week later, the patient will be given ganciclovir, an anti-herpes drug that kills tumor cells containing the herpes gene. The dead cells are absorbed by the body.

Initially, doctors will be concerned not only about how effective the therapy is, but also whether it has toxic side effects. If effective, the treatment could be adapted to treat other malignant tumors.