Media Sugarcoats Fetal Tissue Transplant Failure
By Paul Ranalli, M.D.
The hugely unimpressive outcome of a four-year-long clinical trial that injected brain tissue harvested from aborted babies in an attempt to treat Parkinson's disease was well hidden in recent reports in the mainstream media. Indeed, just reading the headlines of the findings, presented in Toronto at the annual meeting of the American Academy of Neurology, the reader could altogether miss how abysmal were the results of the controversial surgery.
For example, Parkinson's is a disease in which the overwhelming majority of patients are senior citizens. Yet the controversial fetal transplants were found to be ineffective for anyone over 60 years of age. Even among the younger patients in the study, the claimed benefits are limited and qualified.
However, these bottom-line outcomes were well hidden in the rose-tinted press coverage. "Hints of success in fetal cell transplants" (New York Times) and "Parkinson's progress" (Medical Post) stretched the minimally positive results to the breaking point. The Washington Post's statement "Fetal cell implants may benefit younger Parkinson's patients" was at least slightly more realistic.
In fact the supposed benefits were extremely marginal. Were the claims of proponents treated more uncritically, these fetal tissue results could represent the beginning of the end of this unethical chapter in neurological research. Unfortunately, the message may take some time to reach the public, given years of unjustified hype and falsely elevated expectations.
FIRST TIME VIGOROUSLY TESTED
The results were announced in April, 11 years after President Ronald Reagan first banned taxpayer support of fetal tissue transplants from aborted babies and six years after Bill Clinton lifted the ban. The long-awaited study funded to the tune of $5.7 million by the National Institute of Neurological Disorder and Stroke (NINDS) was the first time the much-hyped fetal tissue transplant experiments were subjected to what scientists call "placebo control." Previously, reports of patient benefits lacked a control group against which to measure alleged improvements.
The four-year study was led by Dr. Curt Freed of the University of Colorado in Denver and Dr. Stanley Fahn of Columbia Presbyterian Center in Manhattan. It was highly controversial, not only because of the use of tissue from aborted babies, but also because only half of the patients received the fetal brain tissue.
Once chosen for the study, the 40 patients with advanced Parkinson's disease were assigned randomly to either of two groups. For the "treatment group," the team of doctors from New York and Colorado implanted brain tissue from four aborted fetuses deep in the patients' brains.
A second group (the "placebo" group) underwent a "sham" operation, in which holes were drilled in their skulls. Going in, each patient knew he or she had only a 50-50 chance of actually receiving a fetal tissue implant.
Once the patient's scalp was sewn up and the head bandage applied, there was no outward difference in the appearance of the two groups, ensuring an equal distribution of the "placebo effect." (By this scientists mean the powerful positive benefit on the mind and motivation of a patient who has the belief that an effective treatment has been applied.)
As it turns out, a number of patients from both the placebo group (sham surgery) and the group that received a fetal tissue transplant felt remarkably better after the operation. Dr. Fahn told the New York Times (April 22), "They got this placebo surgery and immediately they felt better." He noted that the feeling of well-being lasted throughout the year of follow-up.
In addition to self-assessment scores in which patients rated how they were doing, a series of thorough examinations were carried out by a team of neurologists who, like the patients, were "blinded" from knowing whether the patient actually received fetal tissue.
Patients were followed for one year, after which the blinding was broken and they were informed whether they had fetal tissue or a sham procedure actually received.
At that point the placebo patients were offered the opportunity to have the fetal transplant at a second operation. Fourteen of the 20 patients who underwent the sham surgery elected to have the surgery.
According to the New York Times, a second team, led by Dr. C. Warren Olanow of the Mt. Sinai School of Medicine in New York, has also received a grant. This group's results will be reported on in two years.
PARKINSON'S DISEASE
Parkinson's disease is generally thought to be caused by the death of cells that make dopamine, a chemical that transmits messages in the brain. It is a slowly degenerative disorder characterized by body tremor, slowness of movement, muscle rigidity, and loss of balance, with onset generally between age 50 and 70, with a peak onset in the early 60s.
For patients over 60, no difference was observed in the tests between the placebo group and the group who received fetal tissue, either on the neurologists' examinations or the patients' own perception of how they were doing. In other words, for the group with the worse cases of Parkinson's, fetal tissue transplantation is a complete failure.
Although there is yet no cure for the disease, which affects an estimated one million Americans, symptoms are initially mild, and can be well treated by a variety of medications, especially for the first five years. Eventually symptoms progress, requiring larger doses of drugs, which are eventually used in combination. Ultimately, the drugs begin to lose their efficacy, and the larger doses required cause unwanted side effects.
It is at this stage that surgical treatments have recently been considered. Aside from the unproven fetal transplants, in fact there are other ethically sound surgical procedures (pallidotomy, deep brain stimulation) which have high success rates, demonstrated in a number of published reports.
A small number of Parkinson's disease patients, like actor Michael J. Fox, first develop symptoms at a much younger age. Mercifully, only an estimated 10% of patients present with symptoms below age 50, half of which (5%) begin below age 40. It usually takes 12-14 years before a patient declines to the stage where drugs afford only limited benefit.
In the NINDS fetal transplant trial, participants had suffered from Parkinson's disease for an average 13.4 years. Thus it is likely that no more than 5% of patients (one in 20) might ever progress to the stage where surgery would be considered below age 60.
"SUCCESS"?
And what of the touted "success" of this trial in patients under 60 years of age? When one looks at the scant data presented, which has still not been subjected to peer-reviewed publication, a magnifying glass is required to discern any functional benefit.
Improvement was noted only in bradykinesia (slowness of movement) and rigidity (stiffness of muscles). Consider the following results in the younger group for whom the fetal transplants are reported to have "worked":
No change in "freezing," a sudden, disturbing loss of all movement.
No improvement in initiating walking.
No improvement in tremor, one of the hallmark signs of Parkinson's disease.
No improvement in walking balance.
No lessening in the number of falls.
No improvement in dyskinesias, the troubling extra body movements that appear in advanced patients.
And this was for the younger group of patients, the group reported as showing benefit. However, even among the younger patients, individual outcomes were unpredictable. "There's enormous individual variation," stated Dr. Gerald Fischbach, director of the NINDS (which funded the study), to the Washington Post (April 22). "This is not a yes or no thing."
Also putting a brave face on the results was Dr. Curt Freed of Colorado, co-director of the study with Dr. Fahn. "We need to reduce the variability of the transplant response," Dr. Freed told the New York Times. Others were more direct. Dr. J. William Langston, president of the Parkinson's Institute, told the Times, "I'm disappointed the results were not more dramatic."
Two patients who received the fetal transplants later died from causes stated to be unrelated to the implant surgery. Autopsies of their brains showed survival and growth of the transplanted fetal cells, at seven months and three years after surgery, respectively.
Proponents of the study used these results to claim the transplant concept is a viable one. However, it turns out that the presence of strong regrowth did not correlate with improvement in function.
Patients in the study were given PET brain scans, which can indicate how much of the depleted brain chemical dopamine is being secreted in various parts of the brain. Two-thirds of patients had at least a 20% improvement in dopamine signal from the transplanted area, in both the older and younger groups. Yet the older patients showed no functional improvement at all.
This led Long Island's Dr. David Eidelberg, who performed the scans, to ask rhetorically, "So why didn't the older group show the improvement the younger group did?" (Medical Post, May 4).
Fortunately for patients with Parkinson's disease, the present and future looks promising along other therapeutic avenues. The sources come either from non-human sources or from within the patient's own brain.
A multi-center human trial utilizing brain tissue from embryonic pigs is underway. Just recently, a startling result was announced from Spain, where researchers working with monkeys extracted cells from a site near the carotid artery in the neck and transplanted them into the monkey's own brain, where they produced the key neuro-chemical dopamine at 35 times the rate of fetal cells. This raises the possibility of a Parkinson's patient being able to be his own donor, utilizing a group of cells with potentially far greater efficacy.
The emerging field of stem cell research (involving stems cells from sources other than human embryos) also looks exciting. Stem cells are developmentally "young," capable of "differentiating" into a number of specialized body cells, such as bone, muscle, and brain cells. While early research found these cells in embryos, new evidence reveals they may lurk in various regions of adult humans.
Parkinson's disease expert Dr. Mark Guttman of the University of Toronto points out that up to 3% of brain cells in a person's gray matter may actually be a form of neural-based stem cell. A pool of these cells can be extracted from brain tissue removed from humans for a variety of therapeutic reasons, then cultured, stored, and eventually encouraged to mature into dopamine-producing cells, suitable for transplant.
Finally subject to the stringent placebo-controlled standards of the rest of medical research, fetal transplantation in Parkinson's disease has been found sorely lacking, even among those for whom there is no ethical dilemma. The research world has largely moved on, turning the page on yet another attempt by abortion advocates to fashion an altruistic spin on modern medicine's most shameful ongoing practice.
Dr. Ranalli is a neurologist at the University of Toronto, and a member of the Advisory Council of the deVeber Institute for Bioethics and Social Research.