Drug repositioning in inflammatory bowel disease and primary sclerosing cholangitis by using genetic information.

Collij, V. (Valerie) (2015) Drug repositioning in inflammatory bowel disease and primary sclerosing cholangitis by using genetic information. thesis, Medicine.

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Abstract

Our aim was to use the knowledge on the genetic background of inflammatory bowel disease (IBD) and primary sclerosing cholangitis (PSC) to identify new drug targets for IBD and/or PSC and identify biologicals or small molecules targeting these genes. We used the candidate genes of IBD and PSC discovered from previous studies and ran them through the Drugbank by using the tool we developed in R. We studied direct protein-protein interactions (PPIs) to gain insight in the networks in which the proteins encoded by IBD and PSC risk genes function (DAVID, KEGG). Finally we did a thorough literature search to select the most promising drugs for IBD and PSC based on the evidence from phase I/II/III RCTs or animal studies (PubMed, Clinicaltrial.gov). First we validated our method by showing that known IBD drugs target IBD risk genes, either directly or through one PPI. Secondly, we identified 46 drugs targeting IBD candidate genes, which have already been investigated in IBD. Thirdly, we identified 25 drugs targeting IBD risk genes, which are already used or investigated in other inflammatory disorders. Fourthly, we identified 26 experimental or investigational drugs whose mechanism looks promising for IBD. Finally we identified 16 drugs targeting PSC candidate genes, either directly or through one PPI. Conclusion: In this study we showed that genes associated with IBD are targeted by approved therapies for IBD and we identified drugs that can possibly be repositioned or further developed for the treatment of IBD and PSC.

Item Type:	Thesis (Thesis)
Supervisor name:	Weersma, Prof. Dr. R.K. and Festen, Dr. E.A.M.
Faculty:	Medical Sciences
Date Deposited:	25 Jun 2020 10:50
Last Modified:	25 Jun 2020 10:50
URI:	https://umcg.studenttheses.ub.rug.nl/id/eprint/1100

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