Gina Kolata/ NY Times
A study that attempted to treat
Parkinson's disease by implanting cells from aborted fetuses into patients'
brains not only failed to show an overall benefit but also revealed a disastrous
side effect, scientists report.
In about 15% of patients, the cells
apparently grew too well, churning out so much of a chemical that controls
movement that the patients writhed and jerked uncontrollably.
The researchers say there is no way to remove or deactivate the
transplanted cells.
On their advice the six patients who
enrolled in the study but who had not yet had the operation have decided to
forego it.
The results, reported in the New
England Journal of Medicine, are a severe blow to what had been considered a
highly promising avenue of research for treating Parkinson's disease,
Alzheimer's disease and other neurological ailments.
The study indicates that the simple
solution of injecting fetal brain cells into a patient's brain may not be enough
to treat complex diseases involving nerve cells and connections that are poorly
understood.
Some say it is time to go back to the
laboratory and to animals before doing any more operations on humans. The findings also may fuel the debate over whether it is
appropriate to use fetal tissue from aborted fetuses to treat diseases.
Despite their disappointment, some
researchers said they hoped that the results would not bring fetal cell research
to a grinding halt. The research
has been controversial because the fetal cells were obtained from abortion
clinics.
"This is still our one great
hope for a cure," said J. William Langston, who is scientific director and
chief executive officer at The Parkinson's Institute in Sunnyvale, CA.
Parkinson's disease occurs when for
unknown reasons, cells of the substantia nigra in the base of the brain die. The hope was that fetal substantia nigra cells might take
over for them. But the study showed
in older patients, the operation had no benefit and in some younger patients,
the transplants brought on nightmarish effects.
Although the paper depicts the
patients with side effect in impassive clinical terms, doctors who have seen
them paint a much different picture. 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 suffer are "absolutely devastating."
"They chew constantly, their
fingers go up and down, their wrists flex and distend," he said.
And the patients writhe and twist, jerk their heads, fling their arms
about."It was tragic, catastrophic," Greene said. "It's a real
nightmare. And we can't selectively
turn it off."
One man was so badly affected that he
could no longer eat and had to use a feeding tube, Greene said.
In another, the condition came and went unpredictably throughout the day,
and when it occurred, the man's speech was unintelligible.
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. And whether it
should be research in people is an open question."
Gerard D. Fischbach, who was director
of the National Institutes of Neurological Disorders and Stroke, which sponsored
the study and is now dean of the faculty of medicine at Columbia University's
College of Physicians and Surgeons said that while the operation had been
promoted by some neurosurgeons as miraculous, this was the first time it was
rigorously evaluated, using sham surgery as a comparison.
Fischbach was the director of the institute only at the end of the study.
"Ad hoc reports of spectacular
results can always occur," Fischbach said.
"But if you do these studies systematically, this is the result you
get."
In the study, researchers led by Curt
R. Freed of the University of Colorado Health Sciences Center in Denver and
Stanley Fahn of Columbia University's College of Physicians and Surgeons,
recruited 40 patients, aged 34 to 75, who had Parkinson's disease for an average
of 14 years. The patients were
randomly assigned to have substantia nigra cells from four fetuses implanted in
their brains or to have sham surgery for comparison.
The surgery took place in Colorado
and the patients were evaluated in New York.
The fetal cell surgery involved drilling four small holes in the
patient's forehead and then inserting long needles through the holes into the
brain and injecting the fetal cells. The
sham surgery involved drilling the holes but not injecting needles into the
brain.
The study's primary measure of success was whether the patients themselves noticed that they were better, as determined by a survey that they mailed in a year later but before they knew whether they had fetal cell implants or not. The study found no difference between the two groups - neither those who had the fetal cell operation nor those who had the sham surgery noticed an improvement in their symptoms.