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Treatment for congenital metabolic disorder with brain dysfunction.

治疗伴有脑功能障碍的先天性代谢紊乱。

基本信息

批准号：
11670791
负责人：
TOKORO Toshiharu
金额：
$ 0.83万
依托单位：
The Jikei University School of Medicine
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1999
资助国家：
日本
起止时间：
1999 至 2000
项目状态：
已结题

项目摘要

1)Treatment for Niemann-Pick disease by Neural Progenitor Cells ;We study the transplantation of neural progenitors as a novel strategy gene therapy and repair in neurodegenerative disorders, Niemann-Pick Disease.Neural progenitor cells (NPC) were injected into left lateral-ventricular space in the 12 Neimann-Pick disease mice model. After 1 month injection of NPC, we found the LacZ activities in brain tissues which is around the lateral-ventricular space and other right side of same area in the brain. But we could not find enough activities of LacZ in vitro. We are now trying to make Neuronal Progenitor Cells which have NPC gene and to injects them into the brain of Niemann-Pick Disease mouse model and its fetus.2)Blood Brain Barrier disruption by cytokine and injection Adenovirus with LacZ gene into brain ; We tried the disruption of BBB by IL-l ＆ TNF-alfa. We injected Adenovirus intra cervical artery of mouse after injection of 20% of manitor. We found faint LacZ activities in the brain around the brain artery but did not any invitro-activities. Mice sometimes have the convulsion after injection of cytokines. we need more experiments to find out the suitable dosage of cytokines and way of injection.3)Try to treat for neurogenarative disorder of mouse fetus ; We injected adenovirus vector which has LacZ gene into fetus amniotic vein of mice. We found LacZ activities in the liver tissues cytochemically but no activities in the brain and other tissues. One of our colleague found that some activities in the brain after injection of adenovirus into amniotic fluid of early stage of gestation, the day 3-7.

1)神经前体细胞治疗尼曼-匹克病：我们研究了神经前体细胞移植作为治疗神经退行性疾病尼曼-匹克病基因治疗和修复的新策略。注射鼻咽癌1个月后，在侧脑室周围及右侧脑组织中可见LacZ活性。但我们在体外找不到足够的LacZ活性。2)细胞因子阻断血脑屏障，脑内注射LacZ基因腺病毒；IL-L、肿瘤坏死因子-α阻断血脑屏障。在小鼠颈动脉注射20%曼诺后，将腺病毒注入小鼠颈动脉。我们发现在大脑动脉周围的大脑中有微弱的LacZ活动，但没有任何体外活动。小鼠在注射细胞因子后有时会出现惊厥。我们还需要更多的实验来寻找合适的细胞因子的剂量和注射方式。3)尝试治疗小鼠胚胎的神经发生障碍；我们将携带LacZ基因的腺病毒载体注射到小鼠的胎儿羊膜静脉中。细胞化学检测发现LacZ在肝组织中有活性，而在脑和其他组织中没有活性。我们的一位同事发现，在妊娠早期，第3-7天，将腺病毒注射到羊水中后，大脑中的一些活动。