Development of a Microphysiological Organ-on-Chip System to Model Amyotrophic

项目摘要 目前尚无散发性肌萎缩侧索硬化症(ALS)的动物模型 以及帕金森氏病(PD)，占所有患者的90%以上。就像遗传学一样 这些疾病还不清楚，也没有针对的药物靶点。这 一项提案旨在使用MPS设备来生产一些第一批零星的ALS和PD 疾病的模型。快速提取患者特异性诱导多能干细胞的研究 早期发病的进展期患者为了获得最大机会看到表型，我们将 将细胞分化为运动神经元或多巴胺神经元--两种主要的细胞类型 感染了这种疾病。使用尖端的电生理技术和 代谢组学结合RNAseq和蛋白质组分析，我们将建立坚实的 与健康对照相比，定义这两种疾病的生物标志物(UG3 阶段)。然后，我们将使用NCATS库开发新的MPS屏幕 基于在UH3相(UG3相)中发现的生物标志物的化合物。 这些研究将共同产生一些零星的神经学模型 使用IPSC技术和MPS技术相结合的疾病。雪松-西奈和 公司有两年的合作关系，这构成了这项提议的基础 以及一个综合的机构平台，在此平台上进行协作，以实现 这项研究。

Project Abstract There are no animal models for sporadic forms of amyotrophic lateral sclerosis (ALS) and Parkinson’s disease (PD) that account for over 90% of all patients. As the genetics of these diseases are not understood there are no drug targets to go for either. This proposal aims to use MPS devices to produce some of the first sporadic ALS and PD models of disease. Using patient specific induced pluripotent stem cells from rapidly progressing patients with early onset for maximal chance of seeing phenotypes, we will differentiate the cells into motor neurons or dopamine neurons – the two major cell types affected in the disease. Using cutting edge electrophysiology techniques and metabalomics combined with RNAseq and proteomic analysis we will establish solid biomarkers that define these two diseases when compared to healthy controls (UG3 phase). We will then develop novel MPS screens using the NCATS library of compounds based on the biomarkers discovered in the UH3 phase (UG3 phase). Together these studies will produce some of the first models of sporadic neurological disease using iPSC technology combined with MPS technology. Cedars-Sinai and the company Emulate have a 2 year relationship that forms the foundation of this proposal and an integrated institutional platform on which to collaborate to achieve the goals of the study.