EMBRYONIC DOPAMINE CELL IMPLANTS FOR PARKINSONISM

晚期帕金森病的药物治疗并不令人满意。病人 患有运动波动，从严重的静止“关闭”时期 到不受控制的异常运动的发作。替换已被销毁 胚胎移植中的多巴胺细胞和神经末梢 中脑可能恢复受调节的多巴胺释放并提供更多 正常的运动控制。人体移植的开放临床试验 科罗拉多大学和其他中心的胚胎多巴胺细胞 已经表明立体定向植入患者的壳核 晚期帕金森氏症(Hoehn和Yahr分期3和4)似乎 对帕金森氏症的许多方面产生改善作用。冰冻 发作、运动障碍发作和动作迟缓已得到缓解，言语和 步行能力有所改善，L-多巴的剂量减少了高达50%。 为了证明这些公开试验的观察结果是有效的，一个 现在需要进行对照研究。通过结合专业知识和专业知识， 年哥伦比亚长老会医院帕金森临床研究中心 纽约大学有胎儿神经移植的经验 科罗拉多大学，我们将进行安慰剂对照，双份 难治性卵巢癌患者胚胎植入的盲法研究 帕金森氏症。病人将按年龄分层。vbl.使用 哥伦比亚大学临床研究中心的密集临床评估 和一种新型的家用计算机和视频录像系统，患者将 在手术前接受至少3个月的监测，并至少 手术后一年。正电子发射计算机断层扫描治疗前后的18F-PET扫描 将进行记录纹状体多巴胺耗竭的严重程度 术前及术后跟踪移植的发展 做手术。在科罗拉多大学，患者将随机 被指派接受胚胎组织植入或假手术 单独做开颅手术。哥伦比亚大学的病人和他们的神经科医生- 长老会不会知道所做的外科手术。组织 受孕后7到8周将使用胚胎。胚胎组织 将与患者进行ABO血型匹配。 使用CT引导的立体定向技术，组织将被注射 双侧进入壳核，单次穿针最多16次 手术。对照组患者将接受胚胎移植 在他们第一次假手术一年后。如果成功，这些 对照实验将证明胎儿中脑多巴胺细胞 植入物可以显著逆转严重的帕金森病和 将确定患者年龄是否会影响移植成功。

Drug therapy of advanced Parkinson's disease is unsatisfactory. Patients suffer from motor fluctuations ranging from severe akinetic "off" periods to episodes of uncontrolled abnormal movements. Replacing destroyed dopamine cells and nerve terminals with transplants of embryonic mesencephalon may restore regulated release of dopamine and provide more normal motor control. Open clinical trials of transplants of human embryonic dopamine cells at the University of Colorado and other centers have shown that stereotactic implants into the putamen of patients with advanced Parkinson's Disease (Hoehn and Yahr Stages 3 and 4) appear to produce amelioration of many aspects of Parkinson's disease. Freezing spells, dyskinetic episodes, and akinesia have been moderated, speech and walking have improved, and doses of L-dopa have been reduced up to 50%. To prove that the observations of these open trials are valid, a controlled study is now required. By combining the expertise of a major Parkinson clinical research center at Columbia-Presbyterian Hospital in New York with the experience of fetal neural transplantation at the University of Colorado, we will perform a placebo controlled, double blind study of embryonic implants into patients with intractable Parkinson's disease. Patients will be stratified by age. Using intensive clinical evaluation in the Clinical Research Center at Columbia and a novel home based computer and video taping system, patients will be monitored for at least 3 months prior to surgery and for a minimum of one year after surgery. Pre and postoperative 18-fluorodopa PET scans will be performed to document the severity of striatal dopamine depletion before surgery and to follow the development of transplants after surgery. At the University of Colorado, patients will be randomly assigned to receive embryonic tissue implants or sham surgery with craniotomy alone. Patients and their neurologists at Columbia- Presbyterian will be unaware of the surgical procedure performed. Tissue from 7 to 8 week post conception embryos will be used. Embryonic tissue will be matched for ABO blood group compatibility with the patient. Using CT guided stereotactic techniques, tissue will be injected bilaterally into putamen with up to 16 needle passes during a single operation. Control patients will be offered transplant with embryonic tissue one year after their initial sham surgery. If successful, these controlled experiments will prove that fetal mesencephalic dopamine cell implants offer significant reversal of severe Parkinson's disease and will establish whether patient age influences transplant success.