Adult Human LIver-derived orgaNoid platForm for modeLing metabolic and FATty livEr Diseases and identifying new therapeutic strategies (INFLATED).
We will use mini liver-organs to model fatty liver diseases to identify new therapeutic strategies
In this project we will combine the expertise of Erasmus MC and Hubrecht Organoid Technology (HUB) further develop our liver organoid non-alcoholic fatty liver disease (NAFLD) model to characterize the disease at a molecular level and to function as a drug screening platform to identify novel compounds that target NAFLD.
The distribution and prevalence of NAFLD in the Dutch adult population is high (22%) and leads eventually to advanced liver damage. Since there is currently no therapy with regulatory approval, patients are subjected to long-term palliative treatments and eventually transplantation surgery and post-transplantation immunosuppressive drugs that need to be taken lifelong. Since the incidence of NAFLD is increasing this disease is expected to be the leading cause of liver transplantation in the near future. Thus, there is an ongoing search for novel drugs that could treat NAFLD. However, this activity has been hampered by the lack of translational and reliable disease models.
In order to address these discrepancies, Erasmus MC and HUB have developed a human liver 3D organoid (organ in a dish) model as a tool to study the healthy and diseased human liver. In this project, we will further develop a liver organoid model of NAFLD which we will use to study disease development and to identify targets for medium throughput drug screening assays.
Upon completion of this project we aim to have established optimal culture conditions for our NAFLD organoid model, to have identified drug-able pathways involved in early and late stages of NAFLD and to have developed our NAFLD organoid model into a validated assay for testing compounds that can potentially prevent or reverse NAFLD. Pharmaceuticals developed using our liver organoid NAFLD screening platform will have the potential to significantly impact patient’s lives by providing longer healthy lives and a reduced need for liver transplants.
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