Freed C R, Greene P E, Breeze R E, Tsai W Y, DuMouchel W, Kao R, Dillon S, Winfield H, Culver S, Trojanowski J Q, Eidelberg D, Fahn S
Division of Clinical Pharmacology, University of Colorado School of Medicine, Denver 80262, USA.
N Engl J Med. 2001 Mar 8;344(10):710-9. doi: 10.1056/NEJM200103083441002.
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.
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 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 received 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.
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 18F-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.
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.
在开放性临床试验中，将人胚胎多巴胺神经元移植到帕金森病患者大脑已证明有益。然而，在对照试验中这种干预是否比假手术更有效尚不清楚。
我们将40例年龄在34至75岁、患有严重帕金森病（平均病程14年）的患者随机分组，分别接受神经细胞移植或假手术；所有患者均采用双盲方式随访一年。在移植受者中，将来自四个胚胎的培养中脑组织双侧植入壳核。在接受假手术的患者中，在颅骨上钻孔但不穿透硬脑膜。主要结局是对疾病严重程度变化的主观整体评分，在一年时按-3.0至3.0的量表评分，负分表示症状恶化，正分表示改善。
移植组一年时改善或恶化的整体评分量表的平均（±标准差）得分为0.0±2.1，假手术组为-0.4±1.7。在较年轻患者（60岁及以下）中，帕金森病的标准化测试显示，与假手术组相比，移植组在早晨服药前进行测试时有显著改善（统一帕金森病评定量表得分P = 0.01；施瓦布和英格兰评分P = 0.006）。移植组的老年患者无显著改善。正电子发射断层扫描或尸检显示，移植组20例患者中有17例检测到移植神经元的纤维长出，表现为18F - 氟多巴摄取增加。在第一年病情改善后，即使在减少或停用左旋多巴剂量后，接受移植的患者中有15%再次出现肌张力障碍和运动障碍。
人胚胎多巴胺神经元移植在严重帕金森病患者体内存活，并在较年轻患者而非老年患者中产生了一定的临床益处。
