Gene Technique Aims to Quiet Parkinson's

By Jamie Talan
Staff Writer

August 19, 2003

A Port Washington man with Parkinson's disease took his place in history Monday as New York surgeons infused genes into
his brain they hope will eventually reduce worsening symptoms.

As his right arm and right leg trembled on the operating table in the neurosurgery suite at New York Presbyterian-Weill
Cornell Center in Manhattan, Nathan Klein, 55, remained awake and in good humor throughout the five-hour procedure, at
one point saying of his surgeon, "I'm going to give him a piece of my mind." This is the first time genes have been
delivered into an adult human brain to change the activity of a specific cell. Gene therapy has been attempted in
children with Canavan's disease, a lethal pediatric brain disorder, and in several Alzheimer's patients. The latter
involved using genes to modify cells in the lab that were then injected into the brain. Those experiment results are
not yet public.

More than 500,000 Americans have Parkinson's disease, which causes tremors and rigidity of the limbs, slows movement
and impairs balance and coordination. Drugs can relieve symptoms but haven't been able to stop disease progression.
Surgically implanting electrodes in the brain can ease symptoms; the new gene therapy approach is similarly designed.
Klein's neurosurgeon, Dr. Michael Kaplitt, developed the approach with Dr. Matthew During of the University of Auckland
in New Zealand.

Excitement at the hospital wasn't universal. In a phone interview, Dr. Warren Olanow, chairman of neurology at Mount
Sinai School of Medicine in Manhattan, said he's not convinced the Cornell team "has selected the right genes or the
right target." "This technique is not offering anything more than can already be accomplished with deep brain
stimulation" by electrode implantation, Olanow said. He fears the new approach could result in suppressed brain tissue
and other involuntary movements.

Klein chose the experimental procedure instead of the established surgery. "I don't like the concept of having
something [a device] inside my body," he said of the increasingly popular electrode technique. Klein, a freelance TV
producer, is the first of 12 patients to receive experimental gene therapy in a study approved by the Food and Drug
Administration to test its safety. Doctors expect to know within two months if it can reduce his symptoms. The genes,
sent deep into the brain in an area called the subthalamic nucleus, are intended to transform one cell type into
another.

"We hope this will quiet the brain," said Kaplitt, who cut through Klein's skull and then threaded a long, thin
electrode through soft tissue to search for a specific set of cells. Dr. Shaik Ubaid recorded the cells' electrical
dance on a computer. When it hit target, the neurons tapped out a steady pattern of electrical activity. The sound was
not unlike heavy rain on glass.

"We're there," Kaplitt said. Kaplitt then threaded a catheter into the area and began the 90-minute infusion.
Throughout the procedure, Klein said he felt fine. Only local anesthetic was used as doctors drilled through his skull
to gain access to the tissue within. He was kept awake so doctors could monitor for problems. None occurred.

Klein's wife, Claire Hamilton, said he has changed since the first symptoms -- the tremors -- began in 1995. He loves
tennis and sailboarding. Over the years, his balance began to fail. Now, his wife walks; he uses a tricycle. "When he
gets up now, he shuffles across the room," Hamilton said. His voice is softer, his words harder to understand.

He enrolled in several experimental drug trials, which he said didn't help. His neurologist, Dr. Andrew Feigin of North
Shore-Long Island Jewish Health Systems, told him about the gene therapy trial. Hamilton said her husband is the
perfect choice for a pioneering patient. "He's very patient and never complains," she said. "Plus, he's young and
nothing else is wrong with him."

The two joked before surgery, after Kaplitt fitted him with a metal frame to keep his head still. "The Frankenstein
look really turns me on," Hamilton told her husband. After five hours, Klein's head was set free. He sat up and smiled.
Then his thumb went up.

SOURCE: Newsday
http://tinyurl.com/kfuz

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