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

项目摘要 目前还没有肌萎缩侧索硬化症（ALS）的动物模型 和帕金森病（PD），占所有患者的90%以上。作为遗传学 这些疾病中的大多数还不清楚，也没有药物靶点。这 一项提案的目的是使用MPS设备来产生一些首批散发性ALS和PD 疾病的模型。使用患者特异性诱导多能干细胞， 对于早期发病的进展患者，为了最大限度地观察表型，我们将 将细胞分化为运动神经元或多巴胺神经元--这两种主要的细胞类型 受疾病影响。使用尖端的电生理技术， 代谢组学结合RNAseq和蛋白质组学分析，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（UG 3 阶段）。然后，我们将使用NCATS库开发新的MPS屏幕， 基于UH 3期（UG 3期）发现的生物标志物的化合物。 这些研究将共同产生一些第一批散发性神经系统疾病模型， 使用iPSC技术结合MPS技术治疗疾病。雪松-西奈和 公司仿真有一个2年的关系，形成了这个建议的基础 以及一个综合的机构平台，可在此平台上合作实现以下目标 书房

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.