FXR-IBD · Industry-Academia exchange to further FXR-based therapeutic intervention and non-invasive diagnosis in Inflammatory Bowel Disease

Inflammatory Bowel Disease (IBD) covers a cluster of disorders characterized by chronic intestinal inflammation which affects approximately 0.2% of the global human population. Current treatment options often fail, are marred by side-effects and undergoing regular endoscopy to monitor and manage the disease is often a burden to the patient.In this study we aim to:1. Develop a novel treatment for IBD, using the recently described anti-inflammatory effects of agonists capable of selectively activating the Farnesoid X nuclear Receptor (FXR) as a pharmaceutical lead.2. Develop a non-invasive diagnostic tool using well-described changes in the gut microbiome of people affected with IBD as a marker to diagnose and monitor disease progression or remission in stool samples.In order to achieve these objectives we will develop 2 novel biological high-throughput screening assays (luciferase- and cofactor interaction-based) with which we can assay selective activity of FXR. These screening assays will be dictated by fundamental scientific insights in FXR-mediated activity and signal transduction. Meanwhile, a new non-invasive microbiome-based diagnostic tool will be generated and validated using feces from well-defined patients with IBD. Ultimately, this project will culminate in proof of principle using first-in-men clinical trials to demonstrate that the anti-inflammatory activity of FXR agonists can be used to treat IBD successfully in vivo.As illustrated above, the development of a new IBD-treatment option and the validation of a novel diagnostic tool require the input of several domains of scientific knowledge, such as medicine, microbiome-genetics, pharmacology and molecular biology. The free flow of ideas between disciplines and unfettered access to specialist expertise will greatly speed up the development of these novel approaches to the treatment and diagnosis of IBD.