  
UPDATE: Dopamine-neuron transplants questioned for older Parkinson's patients
Last Updated: 2001-03-08 12:34:01 EST (Reuters Health)
Incorporates comments of journal editorialists.
WESTPORT, CT (Reuters Health) - In the first double-blind study of embryonic dopamine-neuron transplantation for Parkinson's disease, transplants survived in 85% of patients, regardless of patient age and even without immunosuppression. However, cell transplants produced only limited and transient clinical improvement in subjects under age 60. In older patients, virtually no improvement was seen.
Dr. Curt R. Freed, director of the Neuroscience Center at the University of Colorado Health Sciences Center in Denver, and a multicenter US team report their results in The New England Journal of Medicine for March 8th.
The researchers randomly assigned 40 patients with severe Parkinson's disease, aged 34 to 75, to undergo sham surgery or transplantation of dopamine neurons into the putamen. Except for a patient who was killed in an automobile accident, all patients were followed for 1 year.
Among transplant patients aged 60 or younger, ratings on standardized instruments improved significantly more than in the control group, the research team found. This was not so in the older group, even though the transplants grew equally well in the two age groups.
"What improved was the 'off' condition," Dr. Freed told Reuters Health. "No improvement was evident when the patients were at their best, soon after a dose of medication," Drs. Gerald D. Fischbach and Guy M. McKhann, of the National Institute of Neurological Disorders and Stroke in Bethesda, Maryland, note in an editorial.
"Unfortunately, in about 15% of transplant patients, the dopamine produced by the transplants caused the same excess abnormal movements that the patients had while on drug therapy," Dr. Freed continued.
Drs. Fischbach and McKhann say it is "encouraging" that some of the implanted cells survived and differentiated, but they too are troubled that 15% of implant patients developed "disabling dyskinesias" 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 editorialists write.
Dr. Freed said his team plans to modify the transplant methods. "We are transplanting less tissue to reduce the chance of excess transplant effect. We are also transplanting cells into a new region, the substantia nigra, in addition to the putamen. Animal studies have shown that these dual transplants produce better results."
In order for this type of transplantation to become a routine treatment, the clinical outcome must be less variable, Dr. Freed noted in his comments to Reuters Health. "We need to develop better methods for deciding which patients are likely to benefit. Most important will be techniques for mass-producing dopamine cells in the laboratory to eliminate the need to use fetal cells."
N Engl J Med 2001;344:710-719.
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