First-Ever Gene Therapy Treatment Shows Promise for Parkinson's

Sufferers of Parkinson's disease, from Michael J. Fox to Muhammad Ali, may benefit from a promising but speculative weapon that could one day help doctors battle the degenerative disorder.

For the first time, scientists have used targeted gene therapy to alleviate certain symptoms of Parkinson's, such as difficulties with motor control, speech and balance.

Parkinson's disease is the second most common neurodegenerative disorder (after Alzheimer's) affecting more than 1.5 million people in the United States, most of them above the age of 65.

For now, the implications of the research, which was published in the journal Lancet Thursday, will likely be limited by the small size of the study. But the researchers involved hope that the finding may help turn the tide against the disease.

"This is a milestone for the whole field of gene therapy, and it's encouraging us to do more," said the study's lead author Dr. Michael Kaplitt at NY Presbyterian/Weill Cornell Medical Center in New York, N.Y.

The researchers injected a harmless gene-bearing virus into the brains of 11 men and one woman with moderately severe Parkinson's disease. Using viruses to get genes into people is not new; Kaplitt first used this particular virus 13 years ago.

"Viruses exist in nature mainly to transfer their own genes to the host cell," Kaplitt said in a press release issued Thursday. "So, we modify the [virus] in such a way that the only gene it carries is the one we want to deliver to the therapeutic site."

What is new is the gene that is carried into the cell, known as glutamic acid decaboxylase, or GAD. The GAD gene makes a chemical called GABA, which prevents trigger-happy neurons in the brain from firing excessively and bringing about symptoms.

"GABA is the main inhibitor in the brain," Kaplitt explained to The brains of Parkinson's sufferers have areas of hyperactivity, and are often lacking in GABA.

"Gene therapy would allow the brain to make its own GABA and release it to other parts of the brain."

The researchers targeted the area of the brain that regulates motor activity. But due to federal regulations, they were allowed to target only one side of the brain with the gene therapy.

"Because this was the first time this was being done, federal regulators were concerned that something unusual might happen. That's why ours was a safety study," Kaplitt said.

"So the feeling was that even though most patients have symptoms on both sides of the brain and body, we were only approved to do something to one side of the brain."

The procedure proved to be safe, and 10 out of 12 patients showed improvements in motor function on the side of the body where the gene was injected into the brain within a year.

Several individual patients showed improvements between 40 percent and 65 percent in their motor function scores.

In addition, the researchers scanned the brains of the patients using PET brain scans. Half the patients showed a more normal level of activity in the brain one year after the genes had been injected in their brains.

Effectiveness Testing Needed

The study's authors were quick to point out that their work, a Phase I trial, was meant to show that gene therapy could be safe for patients, not to test it against existing Parkinson's treatments.

"Without question, we can't say for sure that there wasn't a placebo effect from the surgery," Kaplitt said. "The plan is to begin a larger study to look at both sides of the brain to see if the results we see are real."

"This is the first time this has been done in a large way, but it's important to remember that the trial was designed to be a safety trial, not one looking at efficacy," said Dr. Michael Okun, medical director of the National Parkinson Foundation. "Results were promising in terms of safety so far, but we will have to study the long-term effects beyond one year."

Other experts question the outcomes of the study.

"I worry that the response was a nonspecific side effect of doing the surgery," says Dr. Clifford Saper, chairman of the neurology department at Beth Israel Deaconess Medical Center.

Treatment, Not a Cure

So far, there is no cure for Parkinson's, which occurs when certain nerve cells in the brain die or become impaired.

Normally, these cells produce dopamine, a chemical that allows smooth, coordinated function of the body's muscles and movement. When approximately 80 percent of the dopamine-producing cells are damaged, the symptoms of Parkinson's disease appear.

The traditional treatment for Parkinson's disease is the drug Levadopa, or L-dopa. For severe symptoms, an electrical probe commonly called a brain pacemaker is implanted deep into the brain in a surgical technique called deep brain stimulation.

Some say the new gene therapy could have advantages over this type of treatment.

"While the stimulating electrodes have been successful, the operation takes many hours and pacemakers and batteries must be replaced periodically," said Dr. Curt Freed, director of the neurotransplantation program for Parkinson's disease at the University of Colorado School of Medicine.

"The total cost of the operation and equipment often exceeds $100,000. By comparison, this new gene therapy method could be a one-time surgery with improvement that might last a patient's lifetime."

Such a prospect would appeal to many Parkinson's sufferers and their families while they wait for a cure.

"We should be cautiously enthusiastic as we move forward to develop therapies for motor and nonmotor symptoms of Parkinson's," Okun said. "Studies like this are moving us in the right direction."