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Drug Repositioning in Inflammatory Bowel Disease Based on Genetic Information

Collij, Valerie BSc; Festen, Eleonora A. M. MD, PhD; Alberts, Rudi PhD; Weersma, Rinse K. MD, PhD

doi: 10.1097/MIB.0000000000000912
Original Basic Science Articles

Background: Currently, 200 genetic risk loci have been identified for inflammatory bowel disease (IBD). Although these findings have significantly advanced our insight into IBD biology, there has been little progress in translating this knowledge toward clinical practice, like more cost-efficient drug development. Our aim was to use genetic knowledge to identify drugs that warrant further investigation in IBD treatment.

Methods: We hypothesized that proteins encoded by IBD candidate genes are potential IBD drug targets because genetic information can increase successful drug identification. We identified drugs that target the proteins encoded by IBD candidate genes using the DrugBank. We included proteins that are in direct protein–protein interaction with proteins encoded by IBD risk genes. Promising potential IBD drugs were selected based on a manual literature search of all identified drugs (PubMed, ClinicalTrials.gov).

Results: We have identified 113 drugs that could potentially be used in IBD treatment. Fourteen are known IBD drugs, 48 drugs have been, or are being investigated in IBD, 19 are being used or being investigated in other inflammatory disorders treatment, and 32 are investigational new drugs that have not yet been registered for clinical use.

Conclusions: We confirm that proteins encoded by IBD candidate genes are targeted by approved IBD therapies. Furthermore, we show that Food and Drug Administration–approved drugs could possibly be repositioned for IBD treatment. We also identify investigational new drugs that warrant further investigation for IBD treatment. Incorporating this process in IBD drug development will improve the utilization of genetic data and could lead to the improvement of IBD treatment.

Article first published online 6 October 2016.

Department of Gastroenterology and Hepatology, University Medical Centre Groningen, University of Groningen, Groningen, the Netherlands.

Address correspondence to: Rinse K. Weersma, MD, PhD, Department of Gastroenterology and Hepatology, University Medical Center Groningen, University of Groningen, PO Box 30.001, 9700RB Groningen, the Netherlands (e-mail: r.k.weersma@umcg.nl).

Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's Web site (www.ibdjournal.org).

Presented at the Dutch Gastroenterology Society Meeting, March 19, 2015, Veldhoven, the Netherlands.

R. K. Weersma is supported by a VIDI grant (016.136.308) from the Netherlands Organization for Scientific Research (NWO). E. A. M. Festen is financially supported by a Career Development Grant from the Dutch Digestive Foundation (MLDS, CDG 14–04). R. Alberts is supported by a PSC Partners Seeking a Cure grant. V. Collij has no conflict of interest to disclose.

Received March 25, 2016

Accepted July 21, 2016

© Crohn's & Colitis Foundation of America, Inc.
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