Transplantation of embryonic dopamine neurons for severe Parkinson's disease.
Transplantation of embryonic dopamine neurons for severe Parkinson's disease.
复制标题
DOI：
10.1056/nejm200103083441002
复制
发表时间：
2001-03-08
影响因子：
158.5
通讯作者：
Fahn, S
中科院分区：
文献类型：
--
作者：
Freed, CR;Greene, PE;Fahn, S
背景：开放的临床试验证明，将人胚胎多巴胺神经元移植到帕金森病患者的大脑中是有益的。然而，在对照试验中，这种干预措施是否比假手术更有效尚不清楚。方法：我们随机分配40名年龄在34至75岁、患有严重帕金森病（平均病程14年）的患者接受神经细胞移植或进行假手术；所有这些都将以双盲方式进行为期一年的跟踪。在移植受者中，来自四个胚胎的培养中脑组织被植入双侧壳核中。在接受假手术的患者中，头骨上钻孔，但硬脑膜没有穿透。主要结局是对疾病严重程度变化的主观总体评分，一年时评分范围为 -3.0 至 3.0，负分表示症状恶化，阳性评分表示改善。 结果：一年时改善或恶化的总体评分量表的平均 (+/-SD) 分数在移植组中为 0.0+/-2.1，在移植组中为 -0.4+/-1.7。 假手术组。在年轻患者（60 岁或以下）中，帕金森病标准化测试显示，在接受药物治疗前的早晨对患者进行测试时，与假手术组相比，移植组的病情有显着改善（统一帕金森病评定量表评分 P = 0.01；Schwab 和 England 评分 P = 0.006）。移植组的老年患者没有明显改善。移植组 20 名患者中有 17 名检测到来自移植神经元的纤维生长，正电子发射断层扫描或尸检显示 F-18-氟多巴摄取增加。在第一年有所改善后，即使在减少或停止左旋多巴剂量后，仍有 15% 的接受移植的患者再次出现肌张力障碍和运动障碍。结论：人胚胎多巴胺神经元移植在患有严重帕金森病的患者中存活下来，并且对年轻患者产生了一些临床益处，但对老年患者则没有效果。 （N Engl J Med 2001；344：710-9。）版权所有 (C) 2001 马萨诸塞州医学会。
Background: Transplantation of human embryonic dopamine neurons into the brains of patients with Parkinson's disease has proved beneficial in open clinical trials. However, whether this intervention would be more effective than sham surgery in a controlled trial is not known.Methods: We randomly assigned 40 patients who were 34 to 75 years of age and had severe Parkinson's disease (mean duration, 14 years) to receive a transplant of nerve cells or undergo sham surgery; all were to be followed in a double-blind manner for one year. In the transplant recipients, cultured mesencephalic tissue from four embryos was implanted into the putamen bilaterally. In the patients who underwent sham surgery, holes were drilled in the skull but the dura was not penetrated. The primary outcome was a subjective global rating of the change in the severity of disease, scored on a scale of -3.0 to 3.0 at one year, with negative scores indicating a worsening of symptoms and positive scores an improvement.Results: The mean (+/-SD) scores on the global rating scale for improvement or deterioration at one year were 0.0+/-2.1 in the transplantation group and -0.4+/-1.7 in the sham-surgery group. Among younger patients (60 years old or younger), standardized tests of Parkinson's disease revealed significant improvement in the transplantation group as compared with the sham-surgery group when patients were tested in the morning before receiving medication (P = 0.01 for scores on the Unified Parkinson's Disease Rating Scale; P = 0.006 for the Schwab and England score). There was no significant improvement in older patients in the transplantation group. Fiber outgrowth from the transplanted neurons was detected in 17 of the 20 patients in the transplantation group, as indicated by an increase in F-18-fluorodopa uptake on positron-emission tomography or postmortem examination. After improvement in the first year, dystonia and dyskinesias recurred in 15 percent of the patients who received transplants, even after reduction or discontinuation of the dose of levodopa.Conclusions: Human embryonic dopamine-neuron transplants survive in patients with severe Parkinson's disease and result in some clinical benefit in younger but not in older patients. (N Engl J Med 2001;344:710-9.) Copyright (C) 2001 Massachusetts Medical Society.