Washington, DC -- A controversial experimental treatment for Parkinson's in which holes are drilled in the skull and cells from aborted unborn children are implanted in the brain may be less promising than once thought, according to the first controlled trial of the surgery. The news bolster's the statements made by pro-life groups saying that plausible alternatives to using stem cells from unborn children are available and that they can be just as effective.
The study not only failed to show an overall benefit but also revealed a disastrous side effect, scientists report.
In about 15 percent of patients, the implanted cells apparently grew too well, churning out so much of a chemical that controls movement that they writhed and jerked uncontrollably. The researchers say there is no way to remove or deactivate the transplanted cells. On their advice, six patients who enrolled in the study but had not yet had the operation decided to forgo it.
Dr. Paul E. Greene, a neurologist at Columbia University's College of Physicians and Surgeons and a researcher in the study, said the uncontrollable movements some patients developed are "absolutely devastating."
"They chew constantly, their fingers go up and down, their wrists flex and distend," he said."It's a real nightmare. And we can't selectively turn it off." For now, Greene said, his position is clear: "No more fetal transplants. We are absolutely and adamantly convinced that this should be considered for research only."
The study, which was published in this week's New England Journal of Medicine, had raised ethical questions because some participants, for the sake of comparison, underwent sham surgery in which mere indentations were drilled in their heads.
The implanted stem cells - master cells that can develop into many types of tissue - survived and grew into the right kind of brain cells. But they did not help patients older than 60. Most people who suffer from the neurological disease are over 60.
"The fact that [Parkinson's] did not improve in the older patients ... despite the growth and development of dopamine neurons may reflect a lower degree of plasticity of the brain or more diffuse brain disease in the older group," the researchers said.
The transplant technique seemed to help some people under 60, but the benefits were limited and experts disagreed on their significance.
"Improvement was detected only early in the morning after the patients had been without medication overnight," said Drs. Gerald Fischbach and Guy McKhann of the National Institute of Neurological Disorders and Stroke in an accompanying editorial. "No improvement was evident when the patients were at their best, soon after a dose of medicine."
In addition, 15 percent of the transplant recipients who improved during the first year after surgery subsequently developed disabling muscle movements, a side effect characterized as "severe" by Fischbach and McKhann.
Although the editors of the Journal said, "The results do not support the use of this procedure as it was performed in this study," the doctors behind the study say the findings are significant.
Not only did the transplanted cells grow in 85 percent of the patients regardless of their age, but scores on some standardized measures of Parkinson's disease improved by as much as 34 percent, said the chief author of the work, Dr. Curt Freed, director of the University of Colorado Neurotransplantation Center for Parkinson's Disease in Denver.
Freed said that the results from the younger patients are similar to the findings from earlier, smaller-scale transplant experiments, which also involved younger patients. "The fact that our results are consistent with earlier anecdotal reports should be reassuring for everyone working in this field," Freed said.
He said the results already have prompted the team to modify its transplant methods in hopes of getting better results.
"There was tremendous hope that stem cell therapy could be a cure. This study really points out the problems we have to solve before that can happen," said neurologist Dr. J. William Langston, founder of the Parkinson's Institute in Sunnyvale, Calif. Langston said the results indicate that stem cell research for Parkinson's should go back to the animal laboratory.
Parkinson's sufferer Michael J. Fox underwent a different type of surgery -- a thalamotomy, a decades-old operation that destroys overactive, tremor-causing nerve cells by burning or freezing a pea-size spot in the brain.
Parkinson's disease, whose sufferers include former Attorney General Janet Reno and actor Michael J. Fox, is a progressive brain disease marked by tremors, stiffness, slowness and loss of balance. The symptoms grow as the brain loses cells that produce dopamine, a transmitter that carries messages to the nerve cells controlling motion.
The drug L-dopa can treat the symptoms, but the medicine can lead to wild involuntary movements and other side effects, which is why patients often alternate between taking the medicine and going off the drug.
There are also ethical and practical concerns surrounding the therapeutic use of fetal cells. Critics of using such cells, harvested from discarded human embryos, include the pro-life community, which has called the research "gravely immoral." And Fischbach and McKhann write in their editorial: "It is unlikely, for both practical and biological reasons, that transplantation of fragments of embryonic tissue will be the therapy of the future.
"Parkinson's is not a rare disorder: estimates of prevalence in the United States range between 700,000 and 1 million. The number of fetuses required would be staggering, even if only a small proportion of the patients were to receive transplants. Moreover, heterogeneity within tissue fragments is a major barrier to reproducibility," they wrote.