1st Gene Therapy Trial Effective Against Parkinson's

(HealthDay News) -- In an early trial, gene therapy has proven both safe and effective in easing the symptoms of Parkinson's disease, researchers say.

A dozen patients experienced a 25 percent to 30 percent improvement in their total symptoms without any side effects, the U.S. team noted in the June 23 issue of The Lancet.

"Safety and tolerability were met with flying colors. On that level, we are extremely encouraged," said Dr. Matthew During, senior author of the study and professor of molecular biology, immunology and medical genetics at Ohio State University. "All in all, we're very excited, but we have to be a little bit cautious, and we need to do a definitive study with the proper controls."

During completed the study while on the faculty of Weill Medical College of Cornell University in New York City. The trial was conducted with researchers from the Feinstein Institute for Medical Research, part of the North Shore-LIJ Health System, in New York. The study was funded by Neurologix, which was co-founded by During and another study author, Dr. Michael Kaplitt. The two remain as consultants to the company, and Kaplitt's father is chairman of the board of Neurologix.

Parkinson's disease affects some 1.5 million Americans, most of them over the age of 65, although younger patients are also affected, including actor and Parkinson's research advocate Michael J. Fox.

The illness is characterized by a loss of dopamine-producing brain cells, resulting in problems with motor function such as tremors, limb rigidity, slow movement and balance and coordination problems.

There are some treatments but no cure, and, as During pointe out, current treatments are far from ideal.

Patients eventually become resistant to drugs. Deep brain stimulation, which involves placing an electrode deep into the brain, has helped some patients who no longer respond to drugs. But the therapy has side effects and is only partially effective.

"There are wires and a huge battery pack in the chest. It's a bit Frankensteinian, and patients hate it," During said. "There's about a 30 to 40 percent adverse event rate. Although it works, it comes at a significant cost."

"There's an unmet need for Parkinson's disease" treatment, he added.

Gene therapy has shown some promise in different areas of medicine, but there have been lingering concerns about its safety after one patient receiving gene therapy for a rare inherited disorder died in 1999. That case led to a temporary suspension of trials.

The current trial is the first-ever phase I clinical trial looking at gene therapy against Parkinson's disease. The study involved 11 men and one woman, averaging 58 years of age. Participants were divided into three groups of four and given low, medium or high dose injections of the glutamic acid decarboxylase (GAD) gene directly into brain cells. The gene, which is involved in dopamine production, was transferred to the cells using an adeno-associated virus.

There were no side effects associated with the gene therapy and, although the study was not undertaken to show effectiveness, the researchers have noted improvements in movement within three months of the procedure.

Brain scans showed changes in metabolism similar to those that occur after surgery for Parkinson's.

The benefits were equivalent to improvements seen with deep brain stimulation, although deep brain stimulation is given to both sides of the brain, and the gene therapy was only given to one side of the brain because of concerns about side effects.

"It's sort of a proof of concept that the adenovirus vector process is not going to be detrimental for patients or doesn't show signs that it will," said Dr. Gerald Frye, a professor of neuroscience and experimental therapeutics at the Texas A&M Health Science Center College of Medicine. "I am impressed that there weren't a lot of negative things that happened. That's really encouraging."

But Frye added that, right now, it's hard to gauge whether this will be superior or inferior to deep brain stimulation.

"The authors argue that not having to go in and modulate your stimulator is an advantage for gene therapy. But, I would say that the fact that you can modulate stimulation is an advantage," Frye said. "Once you put the gene in, you can't take it back out and turn it up or down."

More information
Learn more about Parkinson's at the National Parkinson Foundation.