Methods of treatment of inflammatory bowel diseases

Inventor's general objective was to investigate the potential role of mucosal thrombin in intestinal inflammation and its mechanisms of action. First, they evaluated whether there is an increased presence of active thrombin in Crohn's Disease (CD): both in patient tissues and in an animal models of IBD. Second, they investigated the effects on mucosal damage and tissue dysfunction resulting from the intracolonic administration of thrombin at a dose comparable to what was detected in the tissue of CD patients. Third, they demonstrated in IBD mouse model that pharmacological inhibition of mucosal thrombin activity is a new therapeutic approach to this debilitating condition, such inhibition, allows to significantly decrease all inflammatory parameters including the fecal bleeding score. Finally, inventors showed that human mucosa- associated commensal biofilms exposed to increasing concentrations of human thrombin exhibited increase in their virulent properties specifically, increased bacterial invasion into human epithelial cell line). So, the present invention relates to a method for preventing or treating inflammatory bowel diseases (IBD) such as Crohn's disease (CD) and ulcerative colitis (UC) by targeting locally the mucosal Thrombin.

Keywords: Mucosal thrombin antagonist, PAR1 antagonist, Inflammatory bowel disease
Patent Application number: PCT/EP2021/074438
Publications:
J Crohns Colitis. 2021 May 4;15(5):787-799. doi: 10.1093/ecco-jcc/jjaa229. Nat Commun. 2019 Jul 19;10(1):3224. doi: 10.1038/s41467-019-11140-w. Br J Pharmacol. 2018 Sep;175(18):3656-3668. doi: 10.1111/bph.14430. Epub 2018 Aug 7.

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