A double‐blind controlled trial of bilateral fetal nigral transplantation in Parkinson's disease

TLDR

A 24‑month double‑blind, placebo‑controlled trial enrolled 34 advanced Parkinson’s patients who were randomized to bilateral fetal nigral transplantation with either one or four donors per side or a sham procedure, with the primary endpoint being change in the motor component of the Unified Parkinson’s Disease Rating Scale in the off state. The study found no overall treatment benefit; while the four‑donor group showed a non‑significant trend toward improvement and mild‑stage patients benefited, most patients deteriorated, 56 % developed dyskinesia, and post‑mortem analysis confirmed dopamine neuron survival, leading the authors to conclude that fetal nigral transplantation is not recommended for Parkinson’s disease.

Abstract

Abstract 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.Ann Neurol 2003;54:403–414