For the second time, cells transplanted from fetuses into brains of Parkinson's patients have failed to show a significant effect.
A paper published online by the Annals of Neurology reports that the second major trial of the technique failed to produce significant improvements in patients' movement but caused serious side effects in more than half the patients. Nevertheless, researchers in the field say they continue to hope that the idea will eventually pan out--perhaps with help from cells grown from embryonic stem cells.
Parkinson's disease is caused by the death of neurons that produce a brain chemical called dopamine. Some researchers have been attempting to treat the disease by implanting dopamine-producing cells collected from the brain tissue of aborted fetuses. The first major study of the technique, led by Curt Freed of the University of Colorado Health Sciences Center in Denver, ended in controversy when it failed to help patients overall and left some with frightening uncontrollable movements (Science, 16 March 2001, p. 2060).
The new study, which was begun before Freed's results were published, was led by neurologist Warren Olanow of the Mount Sinai School of Medicine in New York City. He and his colleagues treated 34 patients. Twenty-three received donor cells, and 11 underwent sham surgery. The surgeons used a different technique than Freed did and followed their subjects for 2 years instead of just 1, but the end result was strikingly similar. Like the previous trial, patients receiving cell transplants did not show significant improvement compared with those who underwent sham surgery. And this time, more than half the patients with implanted cells suffered from uncontrollable movements that did not respond to adjustments in the patient's medication.
The authors conclude that the treatment as practiced today "cannot be recommended as a therapy for Parkinson's disease." Olanow sees a few bright spots, however. He notes that a subset of patients with milder disease did seem to show improvements, although it was too small to be statistically significant. And whereas Freed and colleagues worried that the side effects they saw were caused by runaway cell growth that couldn't be controlled, Olanow and his colleagues believe their patients' tremors, which resemble those that patients suffer when their dopamine doses are just a bit too low, were caused by too little dopamine--a result of not enough new cells surviving.
Despite its disappointing results, the paper "injects some optimism into the field again," says neuroscientist Patrick Brundin of Lund University in Sweden. With dopamine-producing cells derived from human embryonic stem cells, he says, scientists should one day be able to transplant enough cells to help patients.
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