New York, NY, April 21, 1999 – Fetal cell implants help some patients with Parkinson’s disease, especially those over 60. In the first double-blind, placebo-controlled surgical trial testing the safety and effectiveness of fetal dopamine cell implants for the treatment of Parkinson’s disease, many patients who received the implants showed growth of the new brain cells and improvement in their symptoms. Compared to patients who received the placebo operation, transplanted patients were better able to move and perform other activities before taking their medications. The study also showed that there was a great deal of variability in the transplant outcome, so that the benefit for any individual patient was unpredictable. When patients were grouped by age, those under age 60 benefited, while those over age 60 did not.
Results of the study were presented April 21, 1999, at the American Academy of Neurology meeting in Toronto. The study was conducted jointly by researchers at the University of Colorado 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.
“The results of the placebo-controlled study are critical for guiding our research on improving cell transplantation as a treatment for Parkinson’s disease,” said Curt Freed, M.D., professor and director of the Division of Clinical Pharmacology and Toxicology, and director of the Neuroscience Program at the CU-Health Sciences Center. “We are now testing ways to produce a more uniform response and to understand why older patients are more resistant to the effects of the transplant.”
Dr. Freed and his neurosurgical colleague, Robert Breeze, M.D., associate professor of neurosurgery at the CU-Health Science Center, have been researching fetal cell transplantation in the treatment of Parkinson’s disease for more than a decade. In 1988, they performed the first fetal cell implant in the United States.
The unique double-blind surgical experiment was designed in collaboration with Stanley Fahn, M.D., 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, M.D., assistant professor of neurology at the Columbia University College of Physicians & Surgeons and assistant attending neurologist at New York Presbyterian Hospital; and David Eidelberg, M.D., 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 surgical 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 a $4.8 million National Institutes of Health (NIH) grant. The patients were randomized into two groups. Half of the patients had fetal cells implanted in four locations in their brains through a surgical procedure performed under local anesthesia. Patients in the other group had a similar 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. Dr. Eidelberg and his team at North Shore, none of whom knew which patients had received the transplant, then evaluated the patients using a brain imaging technique called Positron Emission Tomography (PET) to study the growth of transplants. Dr. Eidelberg also is director of the PET Imaging Center at North Shore.
Nineteen women and 21 men were enrolled in the trial. Half of the patients were over age 60; the average duration of disease was 13.8 years. 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 significant growth of the implanted cells in about two-thirds of the transplant patients and detected some growth in 17 of the 20 transplant patients. Only one of the 20 placebo 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. Nearly all placebo patients have decided to have the tissue implant.
Parkinson”s disease is a chronic, neurologic disease that impairs mobility. The disease results from the progressive loss of a small number of nerve cells that produce dopamine. While treatment with drugs such as L-dopa has provided substantial relief for most patients with Parkinson”s disease, the drugs tend to lose their effectiveness after five 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 studies showed promising results in some patients with advanced Parkinson”s disease, leading to the collaborative fetal neural transplant program. The program was the first to receive an NIH grant to study fetal tissue implants after a federal ban on funding fetal tissue research was lifted in January 1993.