EMBRYONIC DOPAMINE CELL IMPLANTS FOR PARKINSONISM

胚胎多巴胺细胞植入治疗帕金森症

• 批准号: 2637731
• 负责人: CURT R FREED
• 金额: $ 127.63万
• 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 2000-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2637731
• 关键词: Parkinson's disease; brain metabolism; cell transplantation; clinical research; clinical trials; dihydroxyphenylalanine; dopamine; embryo /fetus tissue transplantation; fluorine; human subject; human therapy evaluation; mesencephalon; nervous system transplantation; neuropsychological tests; neurotransmitter transport; outcomes research; positron emission tomography; radiotracer

During therapy of advanced Parkinsons disease (PD) is unsatisfactory. Patients suffer from motor fluctuations ranging from severe off periods too uncontrolled abnormal movements. Replacing destroyed dopamine cells and nerve terminals with transplants of embryonic mesencepahlon may restore regulated release of dopamine and provide more normal motor control. For the past 3 years, using a double-blind placebo-controlled surgery protocol, we have implanted embryonic mesencephalic tissue containing dopamine cells into the brains of patients with advanced PD. Forty patients under age 75 with PD of at least 7 years duration were randomly assigned to either tissue implants or placebo surgery. Groups were matched for age, gender, and disease severity and were stratified by age. Patients and their examining physicians at Columbia University in New York (CPMC) have been blind to the treatment. After 3 months of baseline evaluations including two inpatient admissions at CPMC, diaries, home videotaping, and fluorodopa PET scans at North Shore University Hospital, patients have undergone a blinded surgical procedure at University of Colorado. Under local anesthesia, all patients have four burrholes through the forehead. In the active transplant group, cultured mesencephalic tissue from four embryos (ED 45-60) is implanted along four 30 to 40 mm needle tracts bilaterally in the putamen. Control patients have no needles penetrating brain. After surgery, blinded evaluations continue for one year. After the blind is broken, placebo surgery patients may elect a tissue implant. By June 1997, 31 of 40 patients have received either an implant or a sham procedure. A total of 24 patients have completed the 12 month followup and have had their blind revealed. All of the first eligible sham surgery patients have requested implant surgery. There have been no perioperative complications. One patient died in an automobile accident 7 months after fetal tissue implant. Immunocytochemical analysis for tyrosine hydroxylase has shown abundant dopamine cell survival in all four needle tracts with about 100,000 dopamine neurons surviving from the four embryos transplanted. Specific Aim 1 is to finish the blinded surgical procedures and the 12-month blinded evaluations of the randomized patients. Specific Aim 2 is to complete the unblinded implant surgeries on patients receiving initial placebo surgery and to follow all patients after unblinding for an additional 4 to 7 years. We postulate that transplant patients will show greater first year clinical improvement than placebo patients. In the long term, we predict that implant patients will show progressive improvement for several years after transplant. Our patient cohort is uniquely able to define the early and long term outcome of neurotransplantation.

晚期帕金森病（PD）的治疗效果不理想。 患者的运动波动范围从严重的关闭 周期太不受控制的异常运动。替换已销毁的 多巴胺细胞和神经末梢与胚胎移植 MesencePahlon可以恢复多巴胺的调节释放， 正常的运动控制 在过去的3年里，使用双盲 根据安慰剂对照手术方案，我们植入了胚胎 含有多巴胺细胞的中脑组织 患者 高级PD 40例75岁以下PD至少7年的患者 持续时间被随机分配到组织植入物或安慰剂组 手术 各组在年龄、性别和疾病严重程度上相匹配， 按年龄分层。 患者和他们的检查医生在 位于纽约的哥伦比亚大学（CPMC）对这种治疗方法视而不见。 3个月的基线评价后，包括2名住院患者 CPMC的入院记录、日记、家庭录像和氟多巴PET扫描 在北岸大学医院，患者接受了一项盲法 科罗拉多大学的外科手术。 在局部麻醉下， 所有病人的前额都有四个钻孔 在活动 移植组，4只胚胎的培养中脑组织（艾德 45-60）沿沿着四个30 - 40 mm针道双侧植入 壳核 对照组患者没有针头穿透大脑。 后 手术后，盲法评价持续一年。 盲人之后是 破裂的安慰剂手术患者可以选择组织植入物。 到了六月 1997年，40名患者中有31名接受了植入或假植入， procedure. 共有24名患者完成了12个月的随访 他们的盲目被揭露了。 所有的第一个合格的假 手术患者要求进行植入手术。 没有发生 围手术期并发症 一个病人死于车祸 胎儿组织植入后7个月。免疫细胞化学分析 酪氨酸羟化酶显示在所有的 四个针道，大约有10万个多巴胺神经元存活， 移植的四个胚胎 具体目标1是完成盲法 外科手术和12个月的盲法评价 随机患者 具体目标2是完成揭盲 对接受初始安慰剂手术的患者进行植入手术， 在揭盲后对所有患者进行额外4至7年的随访。 我们假设移植患者在第一年 临床疗效优于安慰剂组。 从长远来看，我们 预测植入患者将表现出渐进性改善， 移植后几年。 我们的患者队列是唯一能够 确定神经移植的早期和长期结果。