More MS news articles for March 2001

Fetal Brain Cell Transplants Benefit Some Parkinson's Patients

In the first double-blind, placebo-controlled surgical trial testing the safety and effectiveness of fetal dopamine cell implantation for the treatment of Parkinson's disease, most patients who received the implants showed growth of the new brain cells. (NEJM, 3-8-01)

University of Colorado HSC

Fetal Brain Cell Transplants Benefit Some Patients with Parkinson's

In the first double-blind, placebo-controlled surgical trial testing the safety and effectiveness of fetal dopamine cell implantation for the treatment of Parkinson's disease, most patients who received the implants showed growth of the new brain cells, and many had improvement in their symptoms, though some had long-term complications.

The study, which is being published tomorrow in the New England Journal of Medicine, shows that transplanted patients were better able to move and perform other activities before taking their daily medications, compared to patients who received the placebo operation. Among the 40 patients who participated in the trial, 20 received the transplanted fetal cells, and 20 experienced a placebo surgery, in which there was no actual needle penetration of the brain.

Results of the study showed that the transplants grew in 85 percent of patients regardless of age. Standardized tests of Parkinson's disease performed one year after surgery revealed improvements in transplant patients age 60 or younger, but not in older patients. After three years, improvement in the younger patients was greater than after one year. About 15 percent of patients who had initially improved later experienced a recurrence of excess, abnormal movements even after reduction or elimination of levodopa treatment, suggesting that the transplants produced more dopamine than optimal for those patients.

"The results of our study show that fetal dopamine cells have potential value for treating patients with Parkinson's disease," said Curt Freed, MD, professor and head of the Division of Clinical Pharmacology and Toxicology, and director of the Neuroscience Program at the University of Colorado Health Sciences Center. "This research is an important milepost for the ongoing development of cell transplantation as a treatment for Parkinson's. We are now testing ways to produce a better and more uniform response in individual patients and to understand why older patients are more resistant to the effects of the transplant."

In an accompanying editorial in the NEJM, Gerald Fischbach, MD, former director of the National Institute of Neurological Disorders and Stroke (NINDS), and Guy M. McKhann, MD, NINDS associate director for clinical research, recommend caution in interpreting the results of the study, writing: "Disabling dyskinesias appeared in 15 percent of the patients who receive implants, but only in the second year after surgery. These severe side effects appeared in the same patients who had improved during the first year after surgery, and they persisted despite the lowering of the dose of levodopa." The commentators go on to point to the value of the study as an important step in research toward effective therapy for Parkinson's patients.

The study was conducted jointly by researchers at the CU-Health Sciences Center, Denver; Columbia Presbyterian Center of New York Presbyterian Hospital, New York; Columbia University College of Physicians & Surgeons, New York, and North Shore University Hospital, Manhasset, New York.

Dr. Freed and his neurosurgical colleague, Robert Breeze, MD, professor of neurosurgery at the CU-Health Sciences Center, have been researching fetal cell transplantation for more than a decade. In 1988, they performed the first fetal cell implant for Parkinson's disease in the United States.

The unique double-blind surgical experiment was designed in collaboration with Stanley Fahn, MD, director of the Center for Parkinson's Disease and Other Movement Disorders at New York Presbyterian Hospital, and H. Houston Merritt Professor at the Columbia University College of Physicians & Surgeons; Paul Greene, MD, assistant professor of neurology at the Columbia University College of Physicians & Surgeons and assistant attending neurologist at New York Presbyterian Hospital; and David Eidelberg, MD, director of the Functional Brain Imaging Laboratory, director of the Movement Disorder Center at North Shore University Hospital and director of the Movement Disorders Program at the New York Weill Cornell Center of New York Presbyterian Hospital.

"While placebo-controlled drug trials have long been the gold standard to test the value of a new drug, only a few placebo-controlled surgery trials have been conducted," Dr. Fahn said. "In Parkinson's disease, about 30 percent of patients feel better after getting a placebo drug. We found that some patients who had placebo surgery did feel their Parkinson's disease had improved."

Dr. Eidelberg said: "This is a landmark study in the field of Parkinson's research. Using new brain imaging techniques, we are able to understand how clinical improvement is influenced by fetal cell implantation in individual patients."

Forty patients were enrolled in this study, which began in 1995 and was funded by $9 million in National Institutes of Health (NIH) grants. Nineteen women and 21 men were enrolled in the trial. Half of the patients were age 60 or under, and the average duration of disease was 13.8 years. The patients were randomized into two groups. Half of the patients had fetal dopamine cells implanted in four locations in their brains through a surgical procedure performed under local anesthesia. Patients in the other group had a placebo-surgery procedure, in which Dr. Breeze drilled holes in their skulls without penetrating the brain, and no fetal cells were implanted.

Drs. Fahn and Greene enrolled the patients and conducted evaluations without knowing which operation the patients received. They examined patients both on and off their standard medications. They found that the younger group of transplant patients had significant improvement in standardized tests known as the Unified Parkinson's Disease Rating Scale and the Schwab and England activities for daily living scale. Improvement was seen in tests done in the morning before patients had their first dose of levodopa, indicating that the transplants could provide the dopamine needed for movement.

Dr. Eidelberg and his team at North Shore evaluated the patients using a brain imaging technique called Positron Emission Tomography (PET) to study the growth of the transplants. PET scans were conducted prior to surgery and at 12 months after the procedure.

Without knowing which patients received the placebo operation and which received the transplants, Dr. Eidelberg detected growth of the implanted cells in 85 percent of the transplant patients. Only one of the 20 placebo-surgery patients was wrongly thought to have had transplant growth by PET scan.

Autopsies of two patients who died of causes unrelated to the transplant operation showed significant growth of the implanted tissue.

After one year of evaluation and data collection, individual patients and their doctors were then told which procedure they had received. Those who had the placebo operation were given the choice of receiving the fetal implants. Most of the placebo-surgery patients decided to have the transplants (14 out of 20), but as the follow-up and data collection showed the results to be variable, the six remaining patients were advised against transplantation until further research has been completed.

Parkinson's disease is a chronic neurological disease that impairs mobility. The disease results from the progressive loss of a small number of nerve cells that produce dopamine, a chemical neurotransmitter in the brain that is required for normal movement. While treatment with drugs such as levodopa has provided substantial relief for most patients with the disease, the drugs tend to lose their effectiveness after five-to-10 years of use. The goal of the fetal tissue implants is to replace the lost dopamine-producing cells and restore more normal movement to the patients.

Early transplant studies showed promising results in some patients with advanced Parkinson's disease, leading to the collaborative fetal neural transplant program. Future progress in cell transplantation for Parkinson's disease will come from improving survival and growth of dopamine neurons. Equally important is understanding which patients are most likely to respond to transplant. Laboratory production of dopamine cells may prove possible. Such a development could make neurotransplantation available for all patients who could benefit from the procedure.

Sarah Ellis, (303) 315-5571, University of Colorado Health Sciences Center
Carolyn Conway, (212) 305-3900, Columbia University College of Physicians & Surgeons
Mayile Chaffin-Quirai, (212) 305-5587, Columbia Presbyterian Center of New York Presbyterian Hospital
Kathy Robinson, (212) 821-0560, New York Weill Cornell Center of New York Presbyterian Hospital
Elaine Wohl, (516) 465-2600, North Shore University Hospital