THURSDAY, March 17, 2011 (HealthDay News) -- Cutting-edge gene therapy on Parkinson's disease patients significantly improved the tremors, rigidity and other motor skill problems that are hallmarks of the illness, a small new study reports.
The phase 2 study enrolled 45 patients with moderate to advanced Parkinson's disease, with half randomly assigned to receive the gene therapy and half assigned to undergo a "sham" surgery, a mock procedure designed to mimic the experimental approach.
Of the 22 patients who were infused directly into the brain with the glutamic acid decarboxylase (GAD) gene -- which prompts the production of a chemical known as GABA that improves motor control -- half experienced "clinically meaningful improvements" of their symptoms within six months of surgery, the study authors said.
Although several open-label trials on gene therapy have shown promise in treating neurologic disease, the researchers noted that this is the first of its type to be confirmed in a follow-up randomized double-blind trial, a study in which neither the investigators nor the patients knew which patients were receiving the real or sham treatment.
"It's a completely novel therapy -- unlike anything that's currently offered," said co-investigator Dr. Andrew Feigin, an associate investigator at the Center for Neurosciences at Feinstein Institute for Medical Research in Manhasset, N.Y.
"I think we expected to see this effect, but you never know," Feigin added. "I was gratified."
The study is published online March 17 in The Lancet Neurology.
Parkinson's disease affects about one million Americans, most of them over age 50, and is the second most common neurodegenerative disease after Alzheimer's, according to the National Parkinson Foundation.
In addition to confirming results of earlier clinical trials, the treatment didn't have any serious adverse effects on the participants, who ranged in age from 30 to 75, according to the study. The most common mild side-effects related to the treatment were headache (affecting seven of the patients in the infusion group versus two in the sham group) and nausea (six versus two).
Phase 3 trials must be conducted before the U.S. Food and Drug Administration decides whether to approve the treatment for general use.
The therapy, which was done with local anesthesia, used a harmless, inactive virus to deliver the GAD gene into each patient's subthalamic nucleus, a key brain region involving motor function. The gene instructs cells to begin making GABA neurotransmitters to re-establish the normal chemical balance that becomes dysfunctional as the disease progresses.
At the six-month mark, patients in the gene therapy group who had been off their medications for 12 hours showed an average 23.1 percent improvement on a scale used to assess motor function in Parkinson's patients, while placebo patients had a 12.7 percent improvement.
"For the first time, we're one step closer to a gene therapy for any neurological disease, because we passed this hurdle," said study co-author Dr. Michael Kaplitt, vice chairman for research in the department of neurological surgery at Weill Cornell Medical College in New York City.
"I think we're closer than we've ever been to be able to realistically tell patients . . . they can get this done," said Kaplitt, also a co-founder of Neurologix Inc., the Fort Lee, N.J. company that is developing the GAD therapy and that funded the current study. (Several other researchers also have financial ties to Neurologix and/or a patent related to the GAD product.)
Another surgical procedure, known as deep brain stimulation, which permanently implants a nerve control device in the brain, has helped control Parkinson's symptoms in thousands of patients over the last decade. Deep brain stimulation is apparently associated with twice the rate of clinical improvement as the gene therapy, according to background information in the study.
Kaplitt and Feigin said it would be difficult to compare the highly effective deep brain stimulation to gene therapy just yet, but that each procedure offers different benefits.
"In practice . . . there are lots of factors," Feigin said, noting that costs for both may be similar. "Some patients might not want hardware in their brain, or others want tried and true methods. Some want state-of-the-art. So a lot will be determined by the patient."
Dr. Michael S. Okun, national medical director of the National Parkinson Foundation, praised the study, saying it opens the door to "the hope for better symptomatic therapies in Parkinson's disease, though patients should clearly understand their limitations."
Okun added, "The gene therapy approach is clever and different. This is an important study, particularly in terms of safety. It will be important to follow these patients longer to look for delayed benefits and potentially delayed risks."
The U.S. National Institute of Neurological Disorders and Stroke has more on Parkinson's disease.