EMBRYONIC DOPAMINE CELL IMPLANTS FOR PARKINSONISM

胚胎多巴胺细胞植入治疗帕金森症

• 批准号: 2037729
• 负责人: CURT R FREED
• 金额: $ 61.53万
• 依托单位: UNIVERSITY OF COLORADO DENVER
• 依托单位国家: 美国
• 财政年份: 1994
• 资助国家: 美国
• 起止时间: 1994-01-01 至 1998-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2037729
• 关键词: Parkinson's disease; adult human (21+); clinical trials; computer assisted patient care; dopamine; human fetus tissue; human middle age (35-64); human old age (65+); human subject; longitudinal human study; mesencephalon; nervous system transplantation; patient monitoring device; positron emission tomography; putamen; videotape /videodisc

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.

晚期帕金森病的药物治疗效果不理想。 患者 患有运动波动，从严重的运动不能"关闭"期 不受控制的异常运动 替换销毁的 多巴胺细胞和神经末梢与胚胎移植 中脑可以恢复多巴胺的调节释放， 正常的运动控制 人体器官移植的公开临床试验 科罗拉多大学和其他研究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， 晚期帕金森病（Hoehn和Yahr阶段3和4）似乎 改善帕金森病的许多方面。 冻结 法术，运动障碍发作，和运动不能已经缓和，言语和 行走得到改善，左旋多巴的剂量减少了50%。 为了证明这些公开试验的观察结果是有效的， 现在需要进行对照研究。 通过结合专业知识， 哥伦比亚长老会医院帕金森临床研究中心 纽约的经验，胎儿神经移植在 科罗拉多大学，我们将进行安慰剂对照，双 胚胎植入难治性乳腺癌患者的盲法研究 帕金森氏症。 患者将按年龄分层。 使用 哥伦比亚临床研究中心的强化临床评价 和一个新的家庭电脑和录像系统，病人将 在手术前至少监测3个月， 手术后一年。 术前和术后18-氟多巴PET扫描 记录纹状体多巴胺耗竭的严重程度 手术前和手术后跟踪移植的发展 手术 在科罗拉多大学，病人将被随机 分配接受胚胎组织植入或假手术， 开颅手术 哥伦比亚的病人和他们的神经科医生- 长老会不会知道手术过程。 组织 将使用受孕后7 - 8周的胚胎。 胚胎组织 将与患者的ABO血型匹配。 使用CT引导立体定向技术，将组织注射到 在单次穿刺过程中， 操作 对照组患者将接受胚胎移植， 在他们第一次假手术一年后的组织中。 如果成功，这些 对照实验将证明胎儿中脑多巴胺细胞 植入物可显著逆转严重的帕金森病， 将确定患者年龄是否影响移植成功。