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Fetal Cell Grafts Not Effective in Reversing Parkinson's Damage: Presented at SFN

By Roberta Friedman, PhD

NEW ORLEANS, LA -- November 13, 2003 -- Grafts of fetal brain cells failed to repair the neurologic defect in patients Parkinson's disease, with no sustained improvement in symptoms over 2 years, according to a two-center study, with sham surgery as a placebo control.

Investigator Thomas Freeman, professor and medical director of the center for aging and brain repair at the University of South Florida, presented the data here November 11^th at the Society for Neuroscience annual meeting.

Dr. Freeman said, "Based on this profile of safety issues, the use of fetal tissue cannot be recommended" as a treatment for Parkinson's disease. He added,

"These issues may be important when moving on to stem cell based therapies." But noted, "Our findings have to be [referred to] our specific protocol."

Many patients in the study developed dyskinesia when not taking their medication. But the study investigators take this finding as a hopeful sign. They think that the implants produced too little dopamine that resulted in a dyskinesia of dopamine deficit, rather than overabundance, as is usually seen with drug treatment of the disease. The researchers hope that the protocol can be improved by placing more graft material in the brain.

The investigators also speculate that rejection is involved in the graft failure. Patients began to worsen when cyclosporin therapy was stopped, Dr. Freeman said.

The study attempted to obtain a dose response by implanting cells from one donor, or four donors, per brain side, with the target being the putamen. Sham surgery consisted of drilling a partial burr hole that did not penetrate into the dura.

Patients in the study had advanced Parkinson's disease that no longer could be controlled with medication. At least 20% of waking time was spent in the "off" state. Ages of the 36 patients ranged from 35 to 75 years. Motor sub-scores of the Unified Parkinson's Disease Rating Scale, at baseline and at 2 years, in the off state, provided the outcome measure.

Only the single surgeon who performed all the surgeries knew which of the 34 patients had actually been grafted. Patients were followed at two medical centers.

Positron emission tomography, carried out at a third, separate center, showed that grafts produced dopamine, with significantly more of the transmitter present in the substantia nigra region of those grafted, compared to sham operated brains. Most of the increase occurred in the first year after the graft, and continued into the second year.

Sham operated patients, and those receiving material from one donor, had scores on the motor scale that decreased by 9.4 and 3.5 points, respectively. Those grafted from four donors improved by 0.72 points (P = .096).

Post hoc analysis revealed that patients with less advanced disease derived some benefit from the procedure. Those grafted with four donors per side gained 1.5 points on the motor scale while those with a sham operation had a median 21.4-point decline, P = .005).

The improvement for those patients who received material from four donors disappeared after 6 to 9 months, Dr. Freeman said. This is the time at which cyclosporin was discontinued.

"Something happened" when immunosuppression ceased, Dr. Freeman said, adding, "in spite of the blood brain barrier, there probably is a role for long term immunosuppression."

Five patients died during or after the trial of causes unrelated to the study. Autopsy showed more surviving cells, with better integration, for those patients who received grafts from four donors.

Of the 23 patients who received the grafts, 13 developed dyskinesia while off medication. For three patients, symptoms were severe enough to require additional surgery.

Prior to entering the study, none of the participants had had dyskinesia when off medication.


[Study title: Surgical placebo controlled trial of human fetal nigral transplantation in Parkinson's Disease PD). Abstract 656.3]

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