神经移植后亨廷顿舞蹈症患者的运动和认知功能改善

Motor and cognitive improvements in patients with Huntington's disease after neural transplantation.

作者信息

Bachoud-Lévi A C, Rémy P, Nguyen J P, Brugières P, Lefaucheur J P, Bourdet C, Baudic S, Gaura V, Maison P, Haddad B, Boissé M F, Grandmougin T, Jény R, Bartolomeo P, Dalla Barba G, Degos J D, Lisovoski F, Ergis A M, Pailhous E, Cesaro P, Hantraye P, Peschanski M

机构信息

INSERM U 421/IM3 and CHU Henri Mondor-AP/HP, Créteil, France.

出版信息

Lancet. 2000 Dec 9;356(9246):1975-9. doi: 10.1016/s0140-6736(00)03310-9.

DOI:10.1016/s0140-6736(00)03310-9

PMID:11130527

Abstract

BACKGROUND

Huntington's disease is a neurodegenerative disease of genetic origin that mainly affects the striatum. It has severe motor and cognitive consequences and, up to now, no treatment. Motor and cognitive functions can be restored in experimental animal models by means of intrastriatal transplantation of fetal striatal neuroblasts. We explored whether grafts of human fetal striatal tissue could survive and have detectable effects in five patients with mild to moderate Huntington's disease.

METHODS

After 2 years of preoperative assessment, patients were grafted with human fetal neuroblasts into the right striatum then, after a year, the left striatum. Final results were assessed 1 year later on the basis of neurological, neuropsychological, neurophysiological, and psychiatric tests. The results obtained were compared with those of a cohort of 22 untreated patients at similar stages of the disease who were followed up in parallel. Repeated magnetic resonance imaging (MRI) and positron emission tomography (PET) scanning with fluorine-18-labelled fluorodeoxyglucose was also done to assess metabolic activity.

FINDINGS

The final PET-scan assessment showed increased metabolic activity in various subnuclei of the striatum in three of five patients, contrasting with the progressive decline recorded in the two other patients in the series, as seen in patients with untreated Huntington's disease. Small areas of even higher metabolic activity, coregistering with spherical hyposignals on MRI were also present in the same three patients, suggesting that grafts were functional. Accordingly, motor and cognitive functions were improved or maintained within the normal range, and functional benefits were seen in daily-life activities in these three patients, but not in the other two.

INTERPRETATION

Fetal neural allografts could be associated with functional, motor, and cognitive improvements in patients with Huntington's disease.

摘要

背景

亨廷顿舞蹈症是一种遗传性神经退行性疾病，主要影响纹状体。它会导致严重的运动和认知后果，且迄今为止尚无治疗方法。在实验动物模型中，通过纹状体内移植胎儿纹状体神经母细胞可恢复运动和认知功能。我们探究了人类胎儿纹状体组织移植在5例轻度至中度亨廷顿舞蹈症患者中能否存活并产生可检测到的效果。

方法

经过2年的术前评估，患者先被移植人类胎儿神经母细胞至右侧纹状体，1年后再移植至左侧纹状体。1年后根据神经学、神经心理学、神经生理学和精神科测试评估最终结果。将所得结果与一组22例处于疾病相似阶段的未接受治疗的平行随访患者的结果进行比较。还进行了重复的磁共振成像（MRI）和用氟-18标记的氟脱氧葡萄糖进行正电子发射断层扫描（PET）以评估代谢活性。

研究结果

最终的PET扫描评估显示，5例患者中有3例纹状体各亚核的代谢活性增加，这与该系列中另外2例患者（如同未接受治疗的亨廷顿舞蹈症患者那样）记录的代谢活性逐渐下降形成对比。同样是这3例患者，还存在与MRI上球形低信号共定位的代谢活性更高的小区域，提示移植组织具有功能。相应地，这3例患者的运动和认知功能得到改善或维持在正常范围内，且在日常生活活动中出现了功能获益，但另外2例患者未出现这种情况。