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Doctors Try New Gene Therapy Treatment for Parkinson's Disease - 2003-08-21

For the first time ever, doctors are attempting to treat Parkinson's disease with an experimental new method, gene therapy. The first patient, a New York man, has just undergone the treatment.

Until now, gene therapy has never been used to treat the disease known as Parkinson's, which is characterized by tremors, shaking limbs, muscular stiffness and difficulty walking, and affects about 1.5 million Americans. It is caused by excess activity in a small region of the brain, the subthalamic nucleus.

A team of New York doctors has just performed a radical new treatment to try to change that. The method of gene therapy they are experimenting with does not attempt to cure Parkinson's disease, only treat it.

The procedure involves injecting a virus containing gene cells into the affected area of the brain. Since genes cannot penetrate cells directly but viruses can, doctors chose a virus called adeno-associated virus, or AAV, which is harmless to humans. AAV carries the gene into the affected cells.

Dr. Matthew During, a professor of molecular medicine at the University of Auckland in New Zealand, is part of the medical team. He explains that the gene treatment is designed to calm the overstimulated brain activity that causes Parkinson's.

"In Parkinson's disease, essentially, the accelerator is full on and there's no brake and this part of the brain is completely running out of control. What we're doing genetically here is delivering a gene that enables this part of the brain now to quiet its activity and reset the circuitry," he said.

On Tuesday, Nathan Klein became the first person to receive the experimental treatment. He is a 55-year-old New Yorker who suffers from Parkinson's disease and experiences tremors on the right side of his body.

Doctors drilled a coin-sized hole into Mr. Klein's skull, then using a catheter the size of a strand of hair, injected 3.5 billion particles containing the gene into a part of the brain called the subthalamic nucleus, which is where Parkinson's is centered.

A day after his operation, Mr. Klein appears calm and rested. He says he feels fine, but feels no difference in his symptoms so far. Mr. Klein says being a pioneer in the field of gene therapy is a new experience. "It's overwhelming to be the first," he said. "Unfortunately, it will take away from the second and third and fourth."

Doctors at New York-Presbyterian Hospital were encouraged when Mr. Klein tested normal and showed no brain inflammation in an examination Wednesday.

Gene therapy procedures are not without controversy. Last year, a Pennsylvania teenager died during a gene therapy experiment. And in France, research was halted when children undergoing an experimental gene therapy to cure an immune disorder later developed a leukemia-like disease.

The Parkinson's gene treatment has been tested on hundreds of rats and seven primates. Some experts fear that there have not been enough primate trials to prove it works. They say there is a potential danger of viruses spreading through the brain, or of a reaction that could stop brain cells from sending impulses altogether. For example, the already overactive brain could begin to produce too much of the gene product, called GABA.

Dr. Michael Kaplitt is the director of neurosurgery at New York-Presbyterian Hospital. He says doctors have options to counter possible dangers. "We have the potential to back into the same area and put an electrical stimulator in and try to control the activity of this area and there's evidence for that in our animal studies that was published in the October science paper," he said. "Or in the extreme situation we could go back in and destroy this area as is done in some Parkinson's patients and actually eliminate the source of this GABA production."

The medical team emphasized that this is Phase one clinical trial, which means the primary objective is to find out if the treatment is safe for humans, not necessarily effective.

Twelve patients were chosen to participate. Mr. Klein received the lowest dose of the virus and gene, as will the next three patients. The following four patients will receive a higher amount, and the last four will receive the highest. Doctors say they will continue to monitor Mr. Klein's progress and wait one month before performing surgery on the next patient.