A double-blind controlled trial of bilateral fetal nigral transplantation in Parkinson's disease.
Thirty-four patients with advanced Parkinson's disease participated in a prospective 24-month double-blind, placebo-controlled trial of fetal nigral transplantation. Patients were randomized to receive bilateral transplantation with one or four donors per side or a placebo procedure. The primary end point was change between baseline and final visits in motor component of the Unified Parkinson's Disease Rating Scale in the practically defined off state. There was no significant overall treatment effect (p = 0.244). Patients in the placebo and one-donor groups deteriorated by 9.4 +/- 4.25 and 3.5 +/- 4.23 points, respectively, whereas those in the four-donor group improved by 0.72 +/- 4.05 points. Pairwise comparisons were not significant, although the four-donor versus placebo groups yielded a p value of 0.096. Stratification based on disease severity showed a treatment effect in milder patients (p = 0.006). Striatal fluorodopa uptake was significantly increased after transplantation in both groups and robust survival of dopamine neurons was observed at postmortem examination. Fifty-six percent of transplanted patients developed dyskinesia that persisted after overnight withdrawal of dopaminergic medication ("off"-medication dyskinesia). Fetal nigral transplantation currently cannot be recommended as a therapy for PD based on these results.
Olanow
C Warren
CW
Department of Neurology, Mount Sinai School of Medicine, One Gustave L. Levy Place, New York, NY 10029, USA. warren.olanow@mssm.edu
Goetz
Christopher G
CG
Kordower
Jeffrey H
JH
Stoessl
A Jon
AJ
Sossi
Vesna
V
Brin
Mitchell F
MF
Shannon
Kathleen M
KM
Nauert
G Michael
GM
Perl
Daniel P
DP
Godbold
James
J
Freeman
Thomas B
TB
D000328:Adult; D000368:Aged; D016380:Brain Tissue Transplantation / Q000009:adverse effects; D002470:Cell Survival; D004295:Dihydroxyphenylalanine / Q000031:analogs & derivatives* / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism; D004311:Double-Blind Method; D020820:Dyskinesias / Q000209:etiology; D005260:Female; D016332:Fetal Tissue Transplantation / Q000009:adverse effects; D007839:Functional Laterality; D006801:Humans; D008297:Male; D008875:Middle Aged; D009474:Neurons / Q000473:pathology; D010300:Parkinson Disease / Q000150:complications / Q000000981:diagnostic imaging / Q000473:pathology / Q000601:surgery*; D013378:Substantia Nigra / Q000378:metabolism / Q000473:pathology / Q000637:transplantation*; D014055:Tomography, Emission-Computed; D016896:Treatment Outcome
C043437:fluorodopa F 18; D004295:Dihydroxyphenylalanine; D004298:Dopamine