诊断超声击破载Aβ抗体微泡联合NSCs跨BBB治疗阿尔茨海默病的研究

项目名称： 诊断超声击破载Aβ抗体微泡联合NSCs跨BBB治疗阿尔茨海默病的研究

项目编号： No.81471795

项目类型： 面上项目

立项/批准年度： 2015

项目学科： 医药、卫生

项目作者： 徐亚丽

作者单位： 中国人民解放军第三军医大学

项目金额： 73万元

中文摘要： 阿尔茨海默病（Alzheimer's disease,AD）是以皮层、海马区β淀粉样肽（Amyloid β,Aβ）广泛沉积、神经原纤维缠结及不可逆性神经元变性和缺失为主要特征的神经退行性疾病。目前缺乏有效治疗方法，Aβ抗体联合干细胞移植补充缺失神经元为AD替代治疗提供了途径。血脑屏障阻碍治疗性大分子向颅内运输。研究证实聚焦超声联合微泡能有效靶向开放BBB，为大分子物质向颅内输送提供了可行性。前期研究发现诊断超声击破微泡可有效开放海马区BBB促静脉移植骨髓间充质干细胞进入脑缺血灶，改善缺血及神经功能。研究采用体内外AD模型，探索诊断超声击破载Aβ抗体靶向微泡促AD病灶BBB开放、Aβ抗体与神经干细胞（Neural stem cells, NSCs）颅内转运的有效性、安全性及影响因素，利用抗体中和、NSCs再生神经元的双重作用探讨改善AD的有效性，为大分子物质向颅内靶向运输提供安全有效的途径。

中文关键词： 阿尔茨海默病；神经干细胞移植；淀粉样蛋白；超声介导的微泡破坏；血脑屏障

英文摘要： The accumulation of β-amyloid peptide (Aβ) and neurofibrillary tangles in hippocampus and cortex are important pathological features of Alzheimer's disease (AD), which resulted in the neural degeneration and loss. There are no optimal therapeutic tools on AD till now, stem cell transplantation and anti-Aβ monoclonal antibody can repair, replace the degenerated neurons and shows to be a promising approach. Blood brain barrier (BBB) blocks the delivery and transmission of the therapeutic agents like stem cell or antibody to the brain. Microbubble enhanced ultrasonic effect can disrupt the BBB non-invasively, selectively and provides a new method for the delivery of therapeutants to the brain. Previous studies have proved the targeted, effective and safe delivery of intravenous administration of mesenchymal stem cells to unilateral hippocampus under the irradiation of diagnostic ultrasound and microbubble and led to the improvement on brain ischemia and neural dysfunction. The in vitro and in vivo AD models are built, the hippocampus-targeted, non-invasive, successful opening of BBB and delivery of A? monoclonal antibody and neural stem cells (NSCs) are to be investigated under the mediation of diagnostic ultrasound and microbubbles. The combination of the reduction of A? due to the antigen-antibody reaction and the regeneration of neural cells by NSCs plays an important role in the treatment of AD, which might be a good solution for the targeted, safe and successful delivery of the therapeutants to the brain.

英文关键词： Alzheimer's disease;neural stem cells transplantation;amyloid β;ultrasound mediated microbubble destruction;blood brain barrier