Combining Organ-on-Chip Models of Fatty Liver with Computational Biology to Enable Drug Re-purposing

只有十分之一的新药通过临床试验成为批准的药物，这是制药行业的一个重大问题。然而，如果这些失败是由于缺乏疗效，那么就有可能在新的疾病领域重新使用药物。非酒精性脂肪性肝病（NAFLD）在经济发达的国家是一个显著的未满足的医疗需求，仅影响美国人口的5%。目前没有针对脂肪肝疾病的药物治疗，并且该病症是肝硬化和肝细胞癌的前兆，这些病症具有非常差的预后。我们建议结合使用器官芯片技术和计算生物学来确定阿斯利康开发的药物是否可以重新利用并用于治疗脂肪肝疾病。人类NAFLD的器官芯片模型概括了体内疾病病理学，将在全系统范围内进行分析，以生成大型多因素数据集。这些数据将被合并以创建NAFLD中发生的变化的计算网络模型，并将确定有助于疾病进展的潜在药物靶点。我们将探讨阿斯利康提供的药物是否可以重新用于靶向NAFLD中受干扰的途径，最终导致这些药物返回药物开发管道。

Only 1 in 10 of all new drugs makes it through clinical trails to become an approved medicine, which is a signifciant problem for the pharmaceutical industry. However if these failures are due to a lack of efficacy, then it may be possible to repurpose drugs in a new disease areas. Non-alcoholic fatty liver disease (NAFLD) presents a significant unmet medical need in more economically developed nations, affecting up to 5% of the US population alone. There is currently no medical treatment for fatty liver disease and the condition is a precursor to cirrhosis and hepatocellular carcinoma, conditions with very poor prognoses. We are proposing to use a combination of organ-on-chip technology and computational biology to determine if drugs developed by AstraZeneca can be repurposed and used to treat fatty liver disease. Organ-on-chip models of human NAFLD, which recapticulate the in vivo disease pathology, will be analysed on a system-wide scale, to generate a large multifactoral data set. The data will be combined to create computational network models of the changes that occur in NAFLD and potential drug targets will be identified that contribute to disease progression. We will explore whether drugs made available by AstraZeneca can be repurposed to target pathways perturbed in NAFLD, ultimately leading to these drugs being returned to the drug development pipeline.