EMBRYONIC DOPAMINE CELL IMPLANTS FOR PARKINSONISM

在晚期帕金森病(PD)的治疗过程中，效果并不令人满意。 患者的运动波动范围从严重的关闭 周期过长，不受控制的异常运动。替换已被销毁 胚胎移植中的多巴胺细胞和神经末梢 美西帕隆可恢复受调节的多巴胺释放并提供更多 正常的运动控制。在过去的三年里，使用了双盲 安慰剂对照手术方案，我们已经植入了胚胎 含有多巴胺细胞的中脑组织进入脑组织 患有疾病的患者 高级警局。40例75岁以下帕金森病至少7年的患者 持续时间随机分配给组织植入物或安慰剂 做手术。在年龄、性别和疾病严重程度方面进行匹配，并 是按年龄分层的。患者和他们的检查医生在 纽约哥伦比亚大学(CPMC)一直对这种治疗视而不见。 经过3个月的基线评估，包括两名住院患者 CPMC入院、日记、家庭录像和氟多巴正电子发射计算机断层扫描 在北岸大学医院，患者接受了失明治疗 科罗拉多大学的外科手术。在局部麻醉下， 所有患者的额头上都有四个麻孔。在活动中 移植组，培养4个胚胎(ED)的中脑组织 45-60)沿两侧四个30-40 mm的针道植入 壳核。对照组患者无针刺入脑。之后 手术，盲法评估持续一年。在盲人被杀后 破碎的安慰剂手术患者可能会选择组织植入物。到六月 1997年，40名患者中有31人接受了植入物或假体 程序。共有24例患者完成了12个月的随访。 并让人发现了他们的盲目。所有第一批符合条件的假货 手术患者要求进行植入物手术。一直没有 围手术期并发症。一名患者死于车祸 胎儿组织植入后7个月。免疫细胞化学分析 酪氨酸羟化酶显示急性淋巴细胞白血病患者体内有丰富的多巴胺细胞存活。 四个针道，大约100,000个多巴胺神经元存活于 移植的四个胚胎。具体目标1是完成盲人 手术操作和12个月的盲法评估 随机化的病人。具体目标2是完成未失明的 对接受首次安慰剂手术的患者进行种植手术 所有患者在解除失明后再随访4至7年。 我们假设移植患者第一年的表现会更好。 临床改善优于安慰剂患者。从长远来看，我们 预计植入物患者的病情将逐步改善 移植后几年。我们的患者队列是独一无二的 明确神经移植的早期和长期结果。

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.