Hints of Success in Fetal Cell Transplants April 22, 1999: WASHINGTON -- In a small but well-controlled study using tissue from aborted fetuses to treat Parkinson's disease, a team of researchers announced on Wednesday that they have relieved the symptoms of some patients, a discovery that experts say suggests that scientists are on the verge of being able to repair the damaged brain. The study involved only 40 patients, just 20 of whom received the transplants, and the improvements, while significant, were dramatic in only a few. It remains to be seen how long they will last. Those who benefited were better able to move and experienced less stiffness before taking their daily medication. Some were able to switch to less potent drugs. But the findings are tentative. And the experiment, the first of its kind, is certain to inflame a debate that has divided abortion rights advocates and opponents for more than a decade: the questions of whether fetal tissue should be used in medical research, and whether taxpayers should pay for it. For reasons the researchers do not quite understand, they saw the best results in the nine transplant patients who were younger than 60; older patients, who account for the majority of those with Parkinson's, were not helped overall. Some got better but some got worse. The researchers said there was no way to predict who would benefit. But despite the small size of the study and its mixed results, experts said it offered a tantalizing hint that the transplants may someday work. It found that the fetal cells took hold and established new networks to produce a missing neurochemical, dopamine, in the brains of two-thirds of all the transplant recipients, regardless of their age. "Ten or 15 years ago, people would have thought of this as science fiction," said Dr. Gerald Fischbach, director of the National Institute of Neurological Disorder and Stroke, which paid for the study. Given other promising developments in Parkinson's disease, including research involving electrical stimulation of the brain, Fischbach predicted that "within the next 10 years there will be a much more rational and safe and effective means of reversing the dopamine deficit." Of the results announced on Wednesday, Fischbach said, "I think they are extremely promising. My view is that the surgery worked. The cells took. They survived, they were manufacturing the transmitter dopamine." Others were not quite so enthusiastic. "It's mixed," said Dr. J. William Langston, president of the Parkinson's Institute, a nonprofit research organization in Sunnyvale, Calif. "I'm disappointed that the results were not more dramatic. On the other hand, they do show that this seems to be feasible. I think it is a very important first step." The four-year study, which the government said cost $5.7 million, was led by Dr. Curt Freed of the University of Colorado in Denver and Dr. Stanley Fahn of Columbia Presbyterian Center in Manhattan. They announced their findings at a conference of the American Academy of Neurology in Toronto, 11 years after President Reagan first banned taxpayer support for such experiments and six years after President Clinton lifted that ban. The results have not yet been published in a peer-reviewed scientific journal, and in interviews, Freed and Fahn were cautious about their results. They emphasized that questions about the proper dose of cells, and why some patients did better than others, must be be answered before fetal cell transplants can might be put into widespread use. "We need to reduce the variability of the transplant response," Freed said, "namely to know predictably how many cells will survive following transplant and who is the best candidate for a transplant." More than one million Americans suffer from Parkinson's Disease, a degenerative neurological condition that slowly strips patients of control over their own muscles. There is no cure; although the disease can be treated with medication, primarily the drug leva-dopa, it eventually stops working. Patients with advanced cases often lose their ability to walk and speak. For years, Parkinson's patients have watched, frustrated, as their symptoms have worsened while the fetal cell research became caught up in abortion politics. In 1988, Freed began operating on patients with private money, and he continues to to so, he said, in an effort to refine his technique. The operations cost about $35,000 apiece; some have been paid for by patients, some by a Denver philanthropist. But there were difficulties. The fetal tissue is hard to obtain, a problem that might prevent the procedure from being used widely. And until he got government support, Freed said, he was prevented from conducting "a truly high quality study." In 1993, when Clinton lifted the funding ban, he teamed up with Fahn to submit a grant application. The grant was approved the following year, as was one for another team, led by Dr. C. Warren Olanow of the Mt. Sinai School of Medicine in New York. Olanow said he will report his results in two years. The experiments are controversial on two fronts. Not only have they aroused the ire of abortion opponents, they have drawn criticism from ethicists who objected to their placebo-controlled design. In the Freed-Fahn study, each patient underwent neurosurgery: four tiny holes, drilled through the wrinkle lines above the eyebrows into the skull, to clear a pathway to the brain. But only half received injections of dopamine-producing cells into the putamen, the region of the brain that controls movement. In the others, the surgery was a sham, designed to test the placebo response, in which patients get better simply by thinking they have been treated. And indeed, the experiment found a particularly powerful placebo effect in at least three patients in the control group. "They got this placebo surgery and immediately they felt better," Fahn said. "And that feeling of getting better lasted an entire year." Others also responded to the placebo, he said, but for not quite as long. Among them was Lynda McKenzie, a 46-year-old former crafts shop owner from outside Toronto who said she was convinced she had had the real surgery for three or four months after her sham operation. "I felt good afterwards," she said. "I was sure I had it." But the study also left the family of at least one participant feeling desperate, and betrayed. Jack Celnik, a 63-year-old retired nuclear physicist from Lakewood, N.J., was among those in the placebo group. Each was monitored for 13 months and was to be offered the real transplant after that. But given the study's results, doctors are advising Celnik not to have the surgery. "This was like his last hope and his last chance," said his daughter, Gitty Charnas, in a telephone interview on Wednesday. She spoke at a rapid clip, the exasperation and anger evident in her voice. "They used him." Freed said that Celnik's case poses a quandary: Is it proper to perform the surgery, which poses a small risk of hemorrhage and stroke, on a patient who is unlikely to benefit from it, even if that patient demands it? "We pointedly have not operated on any older patients after we became aware of this result," he said. "We are going to have to have a long talk with the people at NIH, as well as the patients." Nineteen women and 21 men enrolled in the trial. The participants had suffered from Parkinson's Disease for an average of 13.8 years when the surgeries began in May 1995. Half the participants were older than 60, but none was older than 75. As measured on a standard scale that rates Parkinson's symptoms, the younger patients who received the transplants demonstrated a 30 percent improvement, Fahn said. They did not relieve the patient's tremors, nor ease the "freezing phenomenon," in which patients freeze up mid-stride. But they lessened slowness and stiffness when patients were off their medicine. Two patients, both older than 60, died of circumstances unrelated to their transplants, one of a heart attack and the other in a car accident. In both cases, Freed said, autopsies showed evidence of cell growth in their brains. By SHERYL GAY STOLBERG Copyright 1999 The New York Times Company janet paterson - 52 now /41 dx /37 onset - [log in to unmask] 613/256/8340 - po box 171/almonte/ontario/k0a 1a0/canada Scan some of My Past Posts at: http://www.newcountry.nu/pd/members/janet/index.htm Mine the PD List Archives at: http://james.parkinsons.org.uk/ Cull Nine Million Pub-Med Medical Studies at: http://www.ncbi.nlm.nih.gov/PubMed/ Comb the 'People With Parkinson's' Web-Ring at: http://www.webring.org/cgi-bin/webring?ring=parkie;list