Fw: Parkinson's Research Is Set Back by Failure of Fetal CellImplants

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From: ilena rose <ilena@...>

Sent: Thursday, March 08, 2001 9:52 PM

Subject: Parkinson's Research Is Set Back by Failure of Fetal CellImplants

> March 8, 2001

> Parkinson's Research Is Set Back by Failure of Fetal Cell Implants

>

> By GINA KOLATA

>

> A carefully controlled study that tried 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 percent 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 that while some patients have similar effects from

> taking too high a dose of their Parkinson's drug, in this case the drugs

did

> not cause the symptoms and there is no way to remove or deactivate the

> transplanted cells.

>

> On the researchers' advice, six patients who enrolled in the study but who

> had not yet had the implantation operation have decided to forgo it.

>

> The results, reported today in The New England Journal of Medicine, are a

> severe blow to what has 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 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 may also fuel the debate over whether it is appropriate to

use

> 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 an abrupt 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 Dr. J.

Langston,

> who is scientific director and chief executive officer at The Parkinson's

> Institute in Sunnyvale, Calif.

>

> Parkinson's disease occurs when cells of the substantia nigra region in

the

> base of the brain die, for unknown reasons. 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 side effects.

>

> Although the paper depicts the patients with the side effects in impassive

> clinical terms, doctors who have seen them paint a very different picture.

>

> Dr. E. Greene, a neurologist at the Columbia University College of

> Physicians and Surgeons and a researcher in the study, said the

> uncontrollable movements some patients suffered were " absolutely

> devastating. "

>

> " They chew constantly, their fingers go up and down, their wrists flex and

> distend, " Dr. Greene said. And the patients writhe and twist, jerk their

> heads, fling their arms about.

>

> " It was tragic, catastrophic, " he 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, Dr. 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, Dr. 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. "

>

> Dr. Gerald D. Fischbach, who was director of the National Institute of

> Neurological Disorders and Stroke, which sponsored the study, said that

> while the operation had been promoted by some neurosurgeons as miraculous,

> this was the first time it was rigorously evaluated. It used sham surgery

as

> a comparison, a controversial and rarely used strategy but one that

> researchers felt was necessary to understand the true effects of the

> operation.

>

> Dr. Fischbach, who is now dean of the faculty of medicine at the Columbia

> University College of Physicians and Surgeons, was the director of the

> institute only at the end of the study.

>

> " Ad hoc reports of spectacular results can always occur, " Dr. Fischbach

> said. " But if you do these studies systematically, this is the result you

> get. "

>

> The surgery, he added, " is not the final solution that people would have

> hoped going into it. "

>

> In the study, researchers, led by Dr. Curt R. Freed of the University of

> Colorado Health Sciences Center in Denver and Dr. Stanley Fahn of the

> Columbia University College of Physicians and Surgeons, recruited 40

> patients, ages 34 to 75, who had 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 fetal cells. The sham surgery involved drilling

the

> holes but not injecting needles into the brain. After a year, the patients

> were told whether they had the fetal cell surgery and, if not, they were

> offered it if they wanted it.

>

> 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 had fetal cell implants

> or a sham operation. The study found no difference between the two

groups -

> neither those who had had the fetal cell operation nor those who had had

the

> sham surgery noticed an improvement in their symptoms.

>

> Other tests, like neurologists' assessments of the patients while they

were

> taking their medication and the patients' assessments of their condition

in

> diaries they kept also showed no effect of the surgery. And there was no

> difference between the two groups in the doses of drugs needed to control

> the disease.

>

> The one glimmer of hope came from assessments by neurologists before the

> patients had had their first dose of medication in the morning. By that

> measure, the 10 patients under age 60 who had had the fetal cell implants

> seemed better than those who had had sham surgery, with less rigidity,

> although their tremor was just as bad.

>

> Dr. Freed hailed that result, saying, " It was a clear-cut improvement. "

>

> And, he added, the fetal cells survived in most patients' brains.

>

> " I would be disappointed if people used a strict clinical trial approach, "

> Dr. Freed said. " This study is about multiple phenomena. "

>

> Others were less enthusiastic, pointing out that finding subgroups after

the

> fact who may have benefited suggests a hypothesis for future studies, not

> evidence of an effect.

>

> " We try to teach everybody that you have to identify beforehand what's the

> primary outcome, " said Dr. Weiner, the director of the land

> Parkinson's Disease and Movement Disorder Center and a professor of

> neurology at the University of land School of Medicine in Baltimore,

> referring to the measure of success determined before the study began. " In

> this case, they picked a subjective assessment by the patients themselves,

> which I think is a very good one. "

>

> And so, Dr. Weiner said, when the patients noticed no improvement, " the

> study was negative. "

>

> In addition, Dr. Langston said, even if a subsequent study confirmed that

> the surgery had an effect on the condition in younger patients before they

> took their medicine in the morning, and even if there was a way of

> preventing the terrible side effect, the operation would still hardly be a

> breakthrough. Parkinson's disease is almost always a disease of the

elderly,

> he noted, adding that well under 10 percent of patients who would be

> candidates for the surgery are younger than 60.

>

> The wiggling and writhing movements first emerged a year after the

> operation, showing up in five of the younger patients who had at first

> appeared to benefit from fetal cell surgery - three who had the operation

in

> the initial phase of the study and two who had it a year later, when they

> learned that they had originally had a sham surgery. While doctors

sometimes

> see such effects in Parkinson's patients, it is caused by giving too much

of

> drugs that act like dopamine in the brain. And it can be controlled by

> reducing the drugs.

>

> In this case, however, drugs were not the culprit. Even when doctors took

> away the drugs, the symptoms persisted.

>

> The fetal implant study had been controversial from the start, both

because

> it included sham surgery and because it used fetal tissue from abortions.

> But many Parkinson's disease experts said it had to be done because

doctors

> were already offering the surgery to patients, and charging them for it,

at

> costs of $40,000 or more, with no evidence that they were helping them.

Yet

> patients, facing a disease in which brain cells slowly and inexorably die

> and in which even the drugs that once controlled their symptoms of tremor

> and rigidity would inevitably fail, took their chances with the operation,

> thinking they had little to lose.

>

> Dr. Freed said he was the first in the United States to offer the

treatment,

> starting in 1988 with a 52-year- old man, who is still alive although, of

> course, he also still has Parkinson's disease.

>

> Dr. Freed continued to offer it to paying patients while he was treating

> those who were part of the federal study and whose procedures were paid

for

> by the study. He said he considered these other operations research

because

> he experimented with different amounts and placements of fetal cells. He

has

> given fetal cell implants to 27 patients, he said, with the most recent

> operation last October.

>

> Dr. Freed said his group was now implanting less fetal tissue and putting

> the tissue in a different area of the brain, hoping to avoid the

devastating

> side effects. But, he said it would be a mistake to stop doing the surgery

> altogether.

>

> " To say that you can't do or shouldn't do human research because the

> research has uncertain outcome, I think would be a bad decision, " Dr.

Freed

> said.

>

> Meanwhile, a second federally financed study of the operation is winding

to

> a close, and some researchers say it is time to go back to animal studies

> and learn more about the complex roles of the brain cells involved in

> Parkinson's disease.

>

> Dr. Weiner said that if a patient came to him today seeking advice, he

would

> say: " The bottom line for patients is that human fetal cell transplants

are

> not currently the best way to go. If you are willing to pay for them, you

> can still have them done. But my advice is you ought not to do this. "

>

> Copyright 2001 The New York Times Company

>

>