The older the brain, the harder it is to integrate the graft. But the PET scans told us that the graft was viable. And it took awhile before the cells worked to improve symptoms.
Manhasset, NY (Vocus) January 1, 2010
Fetal transplant surgery for Parkinson’s disease went on experimentally for more than a decade before it was put to the ultimate test in a double-blind, randomized study. It turned out that only patients under 60-years-old showed any benefit, but some also developed uncontrolled jerking movements that washed away hope for the technique. The findings were the death knell for the promising procedure.
But scientists involved with brain imaging studies of the fetal transplant recipients did not put away their study tools. In fact, they kept bringing the Parkinson’s patients back into the laboratory to take snapshots of their brains over time. And what they have now found, and reported in the latest issue of The Journal of Nuclear Medicine (JNM), is that people over age 60 began to show improvements more than a year after fetal dopamine cells were infused into the brain region damaged by Parkinson’s.
“This was totally surprising,” said David Eidelberg, MD, director of the Center for Neurosciences at The Feinstein Institute for Medical Research in Manhasset, NY. “The use of fetal transplantation for Parkinson’s encountered a good deal of skepticism after five patients in the study (all under age 60) developed dyskinesias.”
Dr. Eidelberg said that the Parkinson’s community basically forgot about the research and turned their attention to other promising techniques.
There were 33 patients, 13 of whom were over age 60 when the cells were infused into their brains. It was a double-blinded study so that 19 patients received the fetal cells and 14 others had a sham surgery and were offered the fetal cell transplant a year later. But by that time, the word had come out about the devastating side effect (the dyskinesias) and some older people opted out of the second surgery.
The Feinstein researchers have now looked at the brains of the transplanted patients two years and four years after the initial infusion of fetal cells. And they learned a few things: Beyond the first five people who developed dyskinesia, none of the other 15 younger people in the study showed signs of the troubling side effect. In about 25 percent of the cases, clinical improvement was noted and the transplanted cells were still working to make the dopamine up to four years later.
They also discovered that the older people gradually got better after the first year and that their improvements continued over the long term. “The older the brain, the harder it is to integrate the graft,” said Dr. Eidelberg. “But the PET scans told us that the graft was viable. And it took awhile before the cells worked to improve symptoms.”
The Feinstein group has identified two different brain networks hard hit in the disease. One is obvious: the motor regions that, when damaged, lead to tremors, rigidity and difficulty initiating movement. The other piece relates to cognition and mood, and there are discrete brain regions that worsen over time. In this study, researchers found that people did better overall on motor functions if they entered the study with their putamen intact – putamen is an area of the brain that governs cognition and mood. Dopamine is the key brain chemical in both these networks and it is critical for motor planning. When dementia sets in, people may have improvements in the motor network, but it isn’t observable because their cognitive network is abnormal and their ability to make plans to move is impaired.
The good news, said Dr. Eidelberg, is that the grafts stayed where they were and delivered dopamine to the tissue. The finding is critical as the field moves to transplant other types of cells, including embryonic stem cells or their ultimate product.
Much of the work for this study was conducted by Feinstein scientist Yilong Ma, MD, in collaboration with Dr. Eidelberg. The fetal cell transplant study was conducted by Paul Greene, MD, and Stanley Fahn, MD, Department of Neurology, Columbia College of Physicians and Surgeons, New York, New York and Robert Breeze, MD, Department of Neurosurgery, University of Colorado School of Medicine, Denver, Colorado; and Curt Freed, MD, Neuroscience Center and Division of Clinical Pharmacology and Toxicology, University of Colorado School of Medicine, Denver, Colorado.
About The Feinstein Institute for Medical Research
Headquartered in Manhasset, NY, The Feinstein Institute for Medical Research (http://www.feinsteininstitute.org) is home to international scientific leaders in cancer, leukemia, lymphoma, Parkinson's disease, Alzheimer’s disease, psychiatric disorders, rheumatoid arthritis, lupus, sepsis, inflammatory bowel disease, diabetes, human genetics, neuroimmunology, and medicinal chemistry. Feinstein researchers are developing new drugs and drug targets, and producing results where science meets the patient, annually enrolling some 10,000 subjects into clinical research programs.
Contact: Jamie Talan, science writer-in-residence,
516-562-1232 or email JTalan3k(at)aol(dot)com
# # #