ST. PAUL, MN -- Brain implants of pig embryonic cells can result in significant clinical improvement in some Parkinson's disease patients, according to a study published in the March 14 issue of Neurology, the American Academy of Neurology's scientific journal.
Parkinson's disease is caused, in part, by a progressive loss of dopamine producing cells in the area of the brain called the striatum. By replacing some of these cells with embryonic dopamine-producing pig cells, the symptoms of Parkinson's disease may improve.
"This is the first study to use pig cells in a human brain," said study author and neurologist Samuel Ellias, MD, PhD, associate professor at Boston University Medical Center. "Previous studies have shown that transplantation of human embryonic cells can be effective in alleviating some symptoms in Parkinson's disease patients. However, the limited availability of human tissue and moral and ethical concerns limit the widespread application of this approach."
These obstacles have caused researchers to look for other tissue sources, including embryonic tissue from animals. The pig is considered a good source for transplantation material because its brain tissue is similar to that of humans.
The study involved 12 patients with advanced Parkinson's disease who had pig embryonic cells surgically implanted at three sites on one side of the brain. All transplant procedures went well and there were no serious side effects related directly to the implants.
Using a Parkinson's disease severity rating scale to measure mobility and the ability to complete common daily activities, ten of the patients' scores improved an average of 19 percent one-year after the transplant. Two patients were not evaluated due to unrelated circumstances. Three patients clinically improved 34 to 51 percent. The initial improvement occurred gradually in some patients, taking up to three or four months. Some patients maintained their improvement beyond one year. Although improvement ratings varied from patient to patient, they were similar to the results observed after the first human embryonic cell transplantation procedures.
A brain scan is used to evaluate implants by measuring dopamine effects in the brain following cell transplantation. Although patients in this study showed clinical improvement through improved mobility, brain scans did not detect cell growth or other specific changes in the patients' brains. This may be due to the limited number of cells injected into a small number of sites.
"Although this study's scan results did not show evidence of a large number of pig dopaminergic neurons, the number of surviving dopaminergic neurons may have been sufficient for clinical improvement in some patients," said Ellias. Successful transplantation from one species to another (xenotransplantation) usually requires immunosuppression for graft survival. Six study patients were given cyclosporine, an agent effective in preventing graft rejection, during surgery and continuously thereafter to improve implant survival. The other six patients received implanted pig cells pretreated with an antibody directed against tissue incompatibility sites on the donor pig cells.
"This anti-rejection technique has been shown to permit graft survival without systemic immunosuppression in animals," explained Ellias. "This is the first experimental use of this technique in humans."
Patients from both groups showed equally significant clinical improvement. However, of the patients with the largest clinical improvement, one did not receive any immunosuppression, which could suggest that this anti-rejection technique may eliminate the need for immunosuppression in some human transplantation procedures.
The donor pigs are raised under controlled quarantined conditions and screened extensively to minimize the risk of transmitting viral or bacterial infections to the patient. Viral agents known to affect humans are screened out. Other viral agents may potentially be transmitted to patients, but have never been shown to infect humans. All study patients tested negative for these infections.
"I am encouraged with the results of this study and feel they represent promise for the future treatment of patients with Parkinson's disease," said Ellias. "Additional trials are underway to more fully assess the clinical benefit and safety of this approach. Patients are receiving transplants with a larger number of pig cells implanted in both sides of the brain. Some of the results will be known later this year."
Parkinson's disease is a chronic neurologic disease that impairs mobility. While treatment with drugs, such as levodopa, have provided substantial relief for most patients with Parkinson's disease, the drugs tend to be less effective in treating fluctuating symptoms after five years.
The study is funded by a joint venture of Genzyme General and Diacrin Inc.
The American Academy of Neurology, an association of more than 16,500 neurologists and neuroscience professionals, is dedicated to improving patient care through education and research.
Editor's Note: Join the American Academy of Neurology in celebrating the progress and promise of brain research during Brain Awareness Week 2000, March 13-19. Brain Awareness Week is an international effort organized by the Dana Alliance for Brain Initiatives and its many partners including the American Academy of Neurology, the National Institutes of Health, and numerous other worldwide government agencies, hospitals, universities, and professional and patient organizations.
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