Non-alcoholic fatty liver disease (NAFLD) is a spectrum of metabolic disorders affecting 25% of our global population. 20% of NAFLD patients go on to develop Non-alcoholic steatohepatitis (NASH), the most severe form of NAFLD, which can result in cirrhosis and liver cancer if left untreated. NASH is characterized by lipid accumulation, infiltration of immune cells, and liver fibrosis. Despite continued research and development efforts, there are currently no approved drug treatments for NASH. Traditional preclinical tests, mainly based on in vivo animal models, have continuously failed to predict human drug efficacy as they inadequately recreate the complexity and multifaceted nature of this human disease. There is a relevancy gap between preclinical models and humans, which human organ-on-a-chip models can address.

Building more predictive, human-relevant models is crucial to successfully bringing efficient anti-NASH therapies to the market. Microphysiological systems (MPS) recapitulate key aspects of human organs’ phenotype, architecture. MPSs extend culture longevity up to a month, enabling studies that were not previously possible, such as the ability to profile phase I and II drug metabolism, mimic key aspects of human diseases, identify potential metabolite-driven toxicity, or detect drug efficacy. In this presentation, we will discuss the use of a liver MPS to model different aspects of clinical NASH and its use to investigate the efficacy and mechanisms of actions of novel NASH therapeutics. 

Learning Objectives:

1. Identify preclinical drug development challenges for NASH studies.

2. Examine a liver MPS model for investigating NASH.

3. Demonstrate how this NASH liver MPS provide translatable insights into drug efficacy for NASH therapeutics.