Spencer D D, Robbins R J, Naftolin F, Marek K L, Vollmer T, Leranth C, Roth R H, Price L H, Gjedde A, Bunney B S
Neural Transplant Program, Yale University School of Medicine, New Haven, Conn. 06510.
N Engl J Med. 1992 Nov 26;327(22):1541-8. doi: 10.1056/NEJM199211263272201.
Parkinson's disease is characterized by the loss of midbrain dopamine neurons that innervate the caudate and the putamen. Studies in animals suggest that fetal dopaminergic neurons can survive transplantation and restore neurologic function. This report compares the clinical results in four case patients with severe Parkinson's disease who underwent stereotaxic implantation of human fetal ventral mesencephalic tissue in one caudate nucleus with the results in a control group of similar subjects assigned at random to a one-year delay in surgery.
Each case patient received cryopreserved tissue from one fetal cadaver (gestational age, 7 to 11 weeks). Before implantation, adjacent midbrain tissue underwent microbiologic, biochemical, and viability testing. Cyclosporine was administered for six months postoperatively.
The procedure was well tolerated. Three case patients showed bilateral improvement on motor tasks, as assessed on videotape, and were more functional in the activities of daily living, as assessed by themselves and neurologists, during both optimal drug therapy and "drug holiday" periods. One case patient, who died after four months from continued disease progression, had striatonigral degeneration at autopsy. In the patients who received transplants, optimal control was achieved with a lower dose of antiparkinsonian medications, whereas the controls required more medication. Positron-emission tomography with [18F]fluorodopa before and after surgery in one patient revealed a bilateral restoration of caudate dopamine synthesis to the range of normal controls, but continued bilateral deficits in the putamen.
Although the case patients continued to be disabled by their disease, unilateral intracaudate grafts of fetal tissue containing dopamine diminished the symptoms and signs of parkinsonism during 18 months of evaluation.
帕金森病的特征是支配尾状核和壳核的中脑多巴胺能神经元丧失。动物研究表明，胎儿多巴胺能神经元可在移植后存活并恢复神经功能。本报告比较了4例重度帕金森病患者的临床结果，这些患者在一侧尾状核接受了立体定向植入人胎儿腹侧中脑组织，同时与一组随机分配延迟一年手术的相似受试者对照组的结果进行了比较。
每位病例患者接受来自一名胎儿尸体（胎龄7至11周）的冷冻保存组织。植入前，对相邻的中脑组织进行微生物学、生物化学和活力测试。术后给予环孢素6个月。
该手术耐受性良好。3例病例患者在录像评估中显示双侧运动任务改善，在最佳药物治疗和“药物假期”期间，自我评估和神经科医生评估显示其日常生活活动功能更强。1例患者在4个月后因疾病持续进展死亡，尸检发现纹状体黑质变性。接受移植的患者用较低剂量的抗帕金森药物即可达到最佳控制，而对照组则需要更多药物。1例患者术前和术后进行的[18F]氟多巴正电子发射断层扫描显示，双侧尾状核多巴胺合成恢复到正常对照范围，但壳核持续存在双侧缺陷。
尽管病例患者仍因疾病而残疾，但在18个月的评估期间，单侧尾状核内移植含多巴胺的胎儿组织减轻了帕金森病的症状和体征。
