Treatment for congenital metabolic disorder with brain dysfunction.

1)神经祖细胞治疗Niemann-Pick病；我们研究神经祖细胞移植作为一种新的策略，基因治疗和修复神经退行性疾病，尼曼-皮克病。将神经祖细胞（NPC）注入12只neimmann - pick病小鼠左侧心室。注射鼻咽癌1个月后，我们发现在脑侧脑室周围和其他右侧相同区域的脑组织中有LacZ活动。但我们在体外没有发现足够的LacZ活性。我们正在尝试制造含有NPC基因的神经祖细胞，并将其注射到尼曼-皮克病小鼠模型及其胎儿的大脑中。2)细胞因子破坏血脑屏障及向脑内注射LacZ基因腺病毒；我们尝试用il - 1和tnf - α破坏血脑屏障。我们在小鼠颈动脉内注射20%的曼尼托后注射腺病毒。我们在大脑动脉周围发现了微弱的LacZ活动，但没有发现任何体外活动。小鼠在注射细胞因子后有时会出现抽搐。我们还需要更多的实验来确定细胞因子的合适剂量和注射方式。3)尝试治疗小鼠胎儿神经发生性疾病；将含有LacZ基因的腺病毒载体注入小鼠胎羊膜静脉。我们发现LacZ在肝组织中有细胞化学活性，但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，大脑中有一些活动。

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.