Parkinson's Gene Therapy Seems to Work

It's been three years since Nathan Klein was the first person to get an experimental gene therapy for Parkinson's disease infused into his brain.

"Before the operation, I was a quivering mass of flesh," Klein, 58, tells WebMD. "With my medications, I am like 80% or 90% better. I am at a point right now where if you didn't know I had Parkinson's disease, you couldn't tell."

Klein is delighted with the treatment -- even though, as the first patient, he got a much lower dose than did the next 11 patients to be treated. Moreover, none of these 12 patients got the full treatment. As a safety precaution, only one side of their brains was treated.

Yet this half-treatment seems to work as well as deep brain stimulation, the best new treatment for Parkinson's disease. And it's safe, reports therapy co-developer Matthew J. During, MD, DSc, of New York-Presbyterian Hospital and Cornell Weill Medical Center.

"These results are just from treating one side of the brain; eventually we will treat both," During tells WebMD. "We hope our results will match or exceed those seen with deep brain stimulation. Even if we just match the deep brain stimulation efficacy, gene therapy would be simpler: no hardware, fewer adverse events. And we have data suggesting this protects against disease progression, so that over time you will see an additional benefit."

During reported the findings in a presentation to the 36th annual meeting of the Society for Neuroscience, held Oct. 14-18 in Atlanta. During, along with Michael G Kaplitt, MD, PhD, co-founded Neurologix Inc., the company developing the gene therapy.
A Pacemaker for the Brain

Brain degeneration in Parkinson's disease overexcites a part of the brain called the subthalamic nucleus (STN). This leads to the abnormal movements, tremor, rigidity, and gait problems that make life miserable for Parkinson's patients.

The therapy created by During and Kaplitt attaches the gene for a chemical messenger, called GAD, to a harmless virus. After infusion into the STN via a thin needle, this genetically engineered virus gets into brain cells and makes them send out GAD signals. It's a signal that tells the brain to calm down.

It doesn't work right away. It takes time for GAD levels to build up.

"Nothing happened for the first week. And then nothing happened for the second week. And then a month, and two months, and then at three months I thought I was a little better, nothing much," Klein says. "It was like watching grass grow. But about six months later, I started feeling a lot better."

During says that Klein's movement problems got about 40% better after treatment. Not all patients have done that well. But those who got the highest dose tended to get the most improvement.

One year after treatment, nine of the 12 patients showed an average improvement of 37% on a measure of Parkinson's disease severity. Five patients had between 40% and 65% improvement.

"We are encouraged the results seem to be maintained over time," During says. "When we look at the other side of the brain, the side we did not treat, we always see worsening of disease. This is a progressive disease. If we hadn't done the treatment, we would expect these patients to be doing significantly worse."
Does It Really Work?

These very encouraging results don't prove anything, During notes. That will depend on a large clinical trial in which participants aren't aware of what treatments they receive and some participants receive no active treatment (placebo). A trial like this is in the planning stages.

Until then, it's just another promising treatment, says Parkinson's researcher Curt R. Freed, MD, head of the division of clinical pharmacology and toxicology at the University of Colorado Health Science Center.

"It is promising at this stage, but like everything else, the proof will be in the pudding," Freed tells WebMD. "Everything will depend on heir clinical trial."

Freed should know. Twenty years ago, he and others started getting intriguing results when they implanted fetal brain cells into the brains of people with Parkinson's disease. These transplanted cells are intended to replace the dopamine-producing cells that die off in Parkinson's disease.

Only about 3% of those transplanted cells survive. But those that survive, Freed reported at the Neuroscience conference, take root and grow -- and keep on growing. If at least 40,000 of the cells survive, it means patients no longer have to take L-dopa, the most important Parkinson's treatment.

The new treatment won't be practical until Freed and colleagues can develop a cell line that will produce a large quantity of fetal brain cells in the laboratory. That, he says, is just a matter of time.

"My interest is getting beyond the use of fetal tissue and using tissues manufactured in the lab," Freed says. "We could have this in patients in the next two to five years."

SOURCES: 36th annual meeting of the Society for Neuroscience, Atlanta, Oct. 14-18, 2006. Matthew J. During, MD, DSc, New York-Presbyterian Hospital/Cornell Weill Medical Center. Curt R. Freed, MD, head, division of clinical pharmacology and toxicology, University of Colorado Health Science Center, Denver. Nathan Klein, New York City.