Bad science revisited

Researcher's Rationalizations for "Devastating" Fetal Tissue Transplant Result Misses the Point: It Doesn't Work

By Paul Ranalli, M.D.

NRL News readers may recall the startling news account that appeared last March, detailing the complete failure of efforts to transplant fetal brain tissue into patients with Parkinson's disease. Not only were there no improvements, but "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," according to the March 6 New York Times.

One of the researchers involved in the study, Dr. Paul Greene, told Gina Kolata of the Times that some of the uncontrollable movements suffered by patients were " absolutely devastating."

"They chew constantly, their fingers go up and down, their wrists flex and distend," Greene said. Moreover, " the patients writhe and twist, jerk their heads, fling their arms about," Kolata wrote.

But now a researcher who helped run the Parkinson's disease fetal tissue transplant experiment that ended so dismally thinks he can explain at least part of the problem. He has reviewed the magnetic resonance imaging brain scans of the five patients who went on to develop this pattern of terrible, uncontrolled body movements (termed "dyskinesias"), and has made a discovery: the grafts were inserted in the wrong place.

"We have learned that it is possible to place grafts where they can cause mischief," said David Eidelberg, a Long Island physician who conducted the brain imaging of the patients during the study, in an interview with a New Scientist reporter published November 13.

He explained that the transplant team headed by Dr. Curt Freed of Colorado had placed the fetal cells into a deep brain nucleus called the putamen. Eidelberg now feels the putamen in these patients was still producing adequate amounts of the brain chemical dopamine, the neurotransmitter which generally runs low in Parkinson's disease which leads to muscle rigidity and slowness of movement.

The insertion of dopamine-producing fetal cells into this region resulted in an excess of dopamine, he surmised, causing the bizarre jerking movements characterized by fellow researcher Dr. Greene as " devastating."

However, Eidelberg's analysis, presented at a recent neuroscience meeting in San Diego, did not address the central result of the NIH-funded fetal tissue trial: the transplants simply did not work!

The "main effect" of the trial, a self-rating by the study patients of their degree of improvement (if any) revealed no difference between those who received a fetal tissue transplant and those who underwent a "sham" operation, in which an identical hole was drilled in the skull, but was not followed by a fetal tissue injection.

The statisticians broke the data down in several different ways and still could not demonstrate any benefit for patients who form the vast majority of Parkinson's disease sufferers' - - those over age 60. In some of the younger patients (who comprise less than 10% of Parkinson's patients this advanced), the researchers tried to show some limited, temporary benefit.

However, some of these patients were the very ones who later lapsed into the horrific pattern of uncontrolled jerking movements. Thus even if future experiments on patients suffering from Parkinson's disease manage to place fetal tissue in the "correct" place, avoiding the abnormal movement side effect, there is still no credible evidence to suggest the tissue would actually make Parkinson's patients better.

Fetal tissue researchers have called, inevitably, for more studies. But the world appears to have passed by the fetal tissue era.

The earliest Swedish and American experiments with fetal tissue are now 15 years old. The ongoing failure of repeated fetal tissue tranplant experiments since then suggests that further refinements in technique will not provide the answer.

It may well be that the entire concept of fetal tissue brain transplantation is simply bad science.

Previous failures to improve the slow, rigid voluntary body movement of Parkinson's disease patients led to calls for experiments using more and more fetal tissue, requiring up to 36 aborted fetuses for every one Parkinson's transplant recipient. However, this latest failure (which was reported in the New England Journal of Medicine last March), accompanied by bizarre muscle overactivity in some, reveals the scientific bankruptcy of this type of thinking.

Fortunately there remains hope for patients with Parkinson's disease.

There are two established neurosurgical procedures - - pallidotomy and deep brain stimulation - - that have already extended the function and lives of hundreds of patients, and are receiving the increasingly laudatory press coverage they deserve. New medications, such as the recently developed drug entecapone, are added each year.

The lasting "legacy" of proponents of fetal tissue transplants may be as purveyors of not only dubious ethical research, but also of false hope.