Print

Print


http://www.eurekalert.org/releases/aane-ptt030700.html


Pig tissue transplant may improve Parkinson's disease

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.