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帕金森病的多巴胺细胞移植:对照临床试验的重要性。

Dopamine cell transplantation for Parkinson's disease: the importance of controlled clinical trials.

机构信息

University of Colorado School of Medicine, Aurora, CO 80045, USA.

出版信息

Neurotherapeutics. 2011 Oct;8(4):549-61. doi: 10.1007/s13311-011-0082-9.

Abstract

Transplantation of human fetal dopamine neurons into the brain of Parkinson's disease patients started in the late 1980s, less than 10 years after experiments in rats showed that embryonic dopamine neurons from a narrow window of development are suitable for transplantation. For human transplantation, the critical stage of development is 6 to 8 weeks after conception. Because putamen is the basal ganglia structure most depleted of dopamine in Parkinson's disease and because it is the structure most closely mapped to the motor cortex, it has been the primary target for neurotransplantation. The double blind trial conducted at the University of Colorado, Columbia University, and North Shore University is the first controlled surgical trial performed in the field of neurosurgery. Results have shown that transplants of fetal dopamine neurons can survive transplantation without immunosuppression and without regard to the age of the patients. Transplants improved objective signs of Parkinson's disease to the best effects of L-DOPA seen preoperatively. Placebo surgery produced no clinical changes. In subjects in whom transplants replaced the need for L-DOPA, the implants replicated the preoperative effects of L-DOPA, including dyskinesias in susceptible patients. Our trial has provided the first controlled evidence that dopamine cell transplants can improve the clinical state of patients with Parkinson's disease.

摘要

人胎多巴胺神经元脑内移植始于 20 世纪 80 年代末,此时距大鼠实验证明胚胎多巴胺神经元在一个狭窄的发育窗口内适合移植还不到 10 年。对于人体移植来说,发育的关键阶段是受孕后 6 至 8 周。由于壳核是帕金森病患者多巴胺缺失最严重的基底神经节结构,而且它与运动皮层的关系最为密切,因此一直是神经移植的主要靶区。科罗拉多大学、哥伦比亚大学和北岸大学进行的这项双盲试验是神经外科领域的首次对照手术试验。结果表明,胎儿多巴胺神经元移植可以在不进行免疫抑制且不考虑患者年龄的情况下存活。移植改善了帕金森病的客观症状,达到了术前左旋多巴的最佳效果。安慰剂手术没有产生任何临床变化。在那些移植替代了左旋多巴需求的患者中,植入物复制了术前左旋多巴的效果,包括易感患者的运动障碍。我们的试验首次提供了对照证据,证明多巴胺细胞移植可以改善帕金森病患者的临床状况。

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