Exploration and preclinical validation of myeloid cell pathways as novel targets and biomarkers for fibrosis development in IBD (FIBRO_TARGET)

Inflammatory Bowel Disease (IBD) are chronic intestinal inflammatory diseases in which recurrent tissue repair progressively leads to fibrosis. This is the irreversible end stage result of excessive fibroblast activation and tissue remodelling that often culminates in luminal stenosis, necessitating surgical intervention, thereby considerably contributing to the socio-economic burden of IBD. Better understanding of the mechanisms contributing to intestinal fibrosis during chronic inflammation is urgently required, because the current therapies diminish inflammation but do not prevent fibrosis.

FIBRO-TARGET will perform translational IBD research to tackle this unmet clinical need by  identifying biomarkers as well as novel targets for fibrosis prevention or treatment. We have multiple lines of experimental evidence that mucosal macrophages and neutrophils modulate intestinal fibrosis. Our aim is to investigate the mechanisms by which these myeloid cells impact on fibrosis development in IBD patients. We will select and validate potential fibrosis targets from already available transcriptomes of specific intestinal macrophage subsets with either pro- or antifibrotic capacities. Moreover, we will investigate how neutrophils influence intestinal fibrosis and we will follow-up on neutrophil inflammasome signalling as an already identified candidate for fibrosis targeting. Along with parallel tissue and serological screens for fibrosis biomarkers in IBD patients, these pre-clinical investigations will propose novel therapeutic approaches to prevent or treat fibrosis in IBD.

The project deliverables will thus include pre-clinically validated druggable targets and early stage drug candidates for companies interested in therapeutic targeting of intestinal or other fibrotic diseases. Therefore, the valorization strategy of FIBRO-TARGET is aimed at follow-up R&D collaborations and/or licensing agreements with our industrial advisory board.