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To: JEB who wrote (49061)	1/28/1999 10:20:00 PM
From: FawnVu	Read Replies (2) \| Respond to of 119973

Newspaper coverage began on CEGE...Starting this evening was Seattle Times....Expect New York, LA, Wahington, and more newspaper coverage tomorrow and through the weekend...CEGE is the mini GERN... Posted at 01:50 p.m. PST; Thursday, January 28, 1999 Study finds new hope for those with Parkinson's disease: gene therapy by Warren King Seattle Times medical reporter Researchers in Seattle and California have taken what could be a major step toward developing gene therapy for one of the most devastating nervous-system disorders: Parkinson's disease. Corrective genes were successfully delivered to certain brain cells of laboratory mice, saving them from dying of a simulated form of the disease and correcting some of their walking difficulties, scientists from the University of Washington and Cell Genesys of Foster City, Calif., report. "I think it shows there's some promise of a therapy. It's very exciting," said Mark Szczypka, one of the UW scientists reporting the research in this month's issue of the journal Neuron. Mice that received the treatment survived for a year - until the experiment ended - without daily injections of a substance that converts to dopamine, a brain chemical that is deficient in the more than 1 million Parkinson's patients nationwide. Animals that did not receive injections or the gene therapy died within three days because dopamine is essential in motivating them to eat. "We think these are dramatic results. What's unique about it is the complete rescue of the genetically deficient animals," said Richard Palmiter, director of the research and a scientist at the Howard Hughes Medical Institute at the UW. The research is the latest example of experimental viral gene therapy, a technology being attempted in a variety of diseases. Scientists nationwide are likely to study the way in which the particular virus was used. The virus type is also being tested in cystic fibrosis, a genetic form of obesity and other diseases. Parkinson's disease results when a large majority of dopamine-producing cells in a certain area of the brain die. Dopamine is a neurotransmitter, a substance that conducts signals among brain cells. Scientists don't know the specific cause, but researchers at the Parkinson's Institute in Sunnyvale, Calif., said this week environmental factors such as pesticide exposure, diet and smoking probably play a major role. Heredity may also be a cause in a small proportion of cases. Symptoms of the disease include muscle rigidity, tremors, slowness of movement, poor balance and problems with walking. Patients commonly are treated with the drug levodopa, which converts to dopamine in the brain. But the drug becomes ineffective in most patients after a few years and often causes side effects such as nausea, dizziness, confusion, drowsiness and insomnia. Brain surgery to alter or stimulate key areas of the brain also is effective in many patients. The gene therapy used by the UW scientists employs a virus to carry a corrective gene into brain regions where dopamine-producing cells reside. They used the virus' natural ability to invade a cell - just as a normal virus, such as a cold germ, moves its genetic material into vulnerable cells. Potentially harmful DNA was removed from the virus used in the treatment. A solution containing the virus - called an "adeno-associated" virus (AAV) - is injected directly into an area of the mice's brains called the striatum. Cell Genesys holds a patent covering gene-therapy products that use the AAV. Mice used in the experiments were genetically altered so they could not produce a critical enzyme needed by brain cells to produce dopamine. Without injections or the gene treatment, they could not move and did not eat or drink. Loss of interest in eating or drinking is not a major symptom of human Parkinson's because patients with the disease don't completely lose the ability to produce dopamine. But Palmiter said the symptoms in the mice are clear evidence of the importance of dopamine to appetite. After a single gene-therapy procedure, the animals' walking ability was somewhat restored, and they began eating and drinking again. "It was one shot, and they were good for life," said Palmiter, UW professor of biochemistry. Palmiter and Szczypka said the research has opened the door to better understanding of how the brain uses dopamine. The next step, they said, is to better understand which specific parts of the brain are most important in behaviors such as eating or moving. The scientists couldn't predict how soon the therapy might be tested in humans. Finding ways to deliver the virus into the brain will be challenging, they said. Other UW scientists at Harborview Medical Center are conducting tests with a system that might be applicable to the therapy. The technology uses magnets to steer a catheter to a target in the brain without damaging vulnerable areas. Warren King's phone message number is 206-464-2247. His e-mail address is: wking@seattletimes.com