Research Yields Clues to Improving Cell Therapy for Parkinson Disease

Abstract

SAN DIEGO—After two airplanes sliced into New York City’s World Trade Center towers on the morning of September 11, thousands of people navigated through smoke, fear, and confusion to emerge from the stricken buildings. Among the survivors was a man with Parkinson disease (PD), an electrician working on the 34th floor of one of the towers, who several years earlier had participated in a study in which fetal dopamine neurons were implanted in his brain. Unimpeded by the slowed movements and shuffling steps that progressively immobilize people with PD, he descended 33 flights of stairs, ran five blocks when the buildings collapsed, and walked three miles to Penn Station to wait for a train to take him home. “This man comes as close to a transplant cure for PD as any we’ve seen,” said Curt Freed, MD, of the University of Colorado School of Medicine, Denver, an investigator on the fetal dopamine cell transplantation study whose work helped his patient cheat death not once but twice—from disaster as well as disease. Freedreportedonrecent findings from a follow-up analysis of the transplantation study at the Society for Neuroscience annual meeting in November. His results and those of others presented at the meeting are suggesting ways to improve treatment for the 1.5 million people in the United States with PD. PREDICTING SUCCESS In 1994, Freed and his colleagues began recruiting 40 patients with advanced PD who were failing drug therapy with levodopa (L-dopa) into a randomized controlled trial to evaluate transplantation of human embryonic dopamine cells for PD. Patients were 34 to 75 years of age, and half were younger than age 60. They were randomly assigned to undergo surgery to replace lost or damaged dopamine-producing neurons with healthy fetal neurons in the putamen region of the brain or sham neurosurgery. Patients were observed in double-blind fashion for 1 year (N Engl J Med. 2001;344:710-719). The study showed not only that the dopamine neurons became incorporated into the brain—at year 1 transplants survived in 85% of patients without immunosuppressive drugs—but that the new cells could in some cases compensate for the loss of dopamine and improve motor symptoms of the disease, said Freed. Age seemed to be a factor in determining response to treatment; patients under age 60 years showed improvements on standardized tests of PD, while older patients did not. In their recent work, Freed and colleagues reviewed the patients 48 months after the transplant surgery. In contrast with the earlier report, the recent analysis indicated that variability in response to L-dopa prior to surgery is a better predictor of patient outcome than age. Freed said that if patients showed at least a 30% improvement in symptoms with L-dopa before surgery, they were more likely to respond to the neuronal transplant regardless of their age. In the future the researchers will use responsiveness to L-dopa as a criterion for determining a patient’s eligibility for transplant surgery.