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First Gene Therapy Attempt to Slow Parkinson's Disease - 2002-10-18

For the first time, gene therapy will be used to try to slow the progression of Parkinson's disease, a neurological disorder marked by severe tremors and muscle stiffness that can make walking or moving almost impossible. Some observers say the procedure could be a significant breakthrough, but others are concerned with ethics.

Parkinson's disease mostly strikes the elderly, affecting approximately one-percent of those over 65. Experts say the disorder, which in the severest cases can leave victims unable to move, is most likely caused by an excess of dopamine, a chemical in the brain that brain cells use to communicate with one another. "Even though we do not know the cause of Parkinson's disease, we are starting to get an idea of what is going wrong and how we can intervene to make the disease [effects] better," said Matew During.

Mattew During is a professor of molecular medicine at the University of Auckland in New Zealand. Professor During is part of a team of researchers, that has obtained permission from U.S. regulators, to try to calm the overactive brain cells of Parkinson's patients that make too much dopamine. "We chose Parkinson's disease because we think it is a very amenable disorder for gene therapy, largely because it involves degeneration of very specific groups within the brain - so, a substance of cells that are well-defined," he said.

Researchers will put a gene called GAD into a virus that most people have been exposed to and has been demonstrated as safe. They will then inject the genetic compound into the diseased region of Parkinson's patients.

GAD makes a protein called GABA that in healthy people regulates the production of dopamine.

Researchers hope the gene therapy will "reset" the overactive dopamine-producing brain cells of Parkinson's patients, restoring more normal movement.

In experiments with rats, Professor During says the therapy worked very well, as measured by electrodes placed in the brains of living animals that measured the release of GABA. "In the rat studies, the gene stays on for the life of the animal, essentially," he said. "And they continued to do well."

The researchers described their gene therapy work with rats in the journal Science.

Other treatments have been developed to help Parkinson's patients, but they have had mixed success. Michael Kaplitt is a brain surgeon, at Weill -Cornell Medical College in New York City, who is part of the research team.

Dr. Kaplitt implants what are know as deep brain stimulation devices. The device uses a small amount of electrical current to coax nerve cells to stop producing too much dopamine. But he says deep brain stimulation devices have their drawbacks. "They actually do help a large number of Parkinson's patients quite a bit," he said. "But there are some limitations to have hardware put in your body, the hardware can get infected. There are other potential problems with the hardware in terms of its breaking, etc."

Dr. Kaplitt will be infusing the gene therapy into the brains of a dozen hand-picked patients with Parkinson's who have failed other therapies. He hopes it will be an extension of the benefits of electrical stimulation, without the side effects.

There have been several highly publicized cases in which gene therapy went awry, including one this summer in France. According to Arthur Caplin of the Center for Bioethics at the University of Pennsylvania, investigators were using gene therapy to treat children who were born with an immune deficiency disorder known as "bubble boy" disease. "And it worked," said Arthur Caplan. "But one of the 10 subjects got leukemia, a kind of a cancer. And everybody believed that is because the genes wound up in the wrong place in that boy. So, is it positive that this experiment is underway? Absolutely. Is it still going to take awhile to figure out whether [it's] doing good? Yes. I think this gene therapy experiment is very much worth doing, but I would not want to say, you know, we are going to have a handle on this disease until we see a lot more subjects tested."

The three-phase clinical trial will initially test the safety of the gene therapy in Parkinson's patients. If it is safe, then the next two phases will test safety and effectiveness in larger groups of patients.