A double-blind controlled trial of bilateral fetal nigral transplantation in Parkinson's disease
A double-blind controlled trial of bilateral fetal nigral transplantation in Parkinson's disease
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DOI：
10.1002/ana.10720
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发表时间：
2003-09-01
影响因子：
11.2
通讯作者：
Freeman, TB
中科院分区：
文献类型：
--
作者：
Olanow, CW;Goetz, CG;Freeman, TB
34 名晚期帕金森病患者参加了一项为期 24 个月的前瞻性双盲、安慰剂对照胎儿黑质移植试验。患者被随机分配接受双侧移植（每侧有一名或四名捐赠者）或安慰剂手术。主要终点是在实际定义的关闭状态下统一帕金森病评定量表的运动部分在基线和最终就诊之间的变化。总体治疗效果不显着（p = 0.244）。安慰剂组和单供体组的患者病情分别恶化了 9.4 +/- 4.25 分和 3.5 +/- 4.23 分，而四供体组的患者则改善了 0.72 +/- 4.05 分。尽管四供体组与安慰剂组的 p 值为 0.096，但两两比较并不显着。根据疾病严重程度的分层显示出对较轻患者的治疗效果（p = 0.006）。两组移植后纹状体氟多巴摄取均显着增加，尸检时观察到多巴胺神经元的存活率良好。 56% 的移植患者出现运动障碍，并在停药过夜后持续存在（“停药”运动障碍）。根据这些结果，目前不能推荐胎儿黑质移植作为帕金森病的治疗方法。
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.