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

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.