Back to Search
Start Over
Computational repositioning of the anticonvulsant topiramate for inflammatory bowel disease.
- Source :
-
Science translational medicine [Sci Transl Med] 2011 Aug 17; Vol. 3 (96), pp. 96ra76. - Publication Year :
- 2011
-
Abstract
- Inflammatory bowel disease (IBD) is a chronic inflammatory disorder of the gastrointestinal tract for which there are few safe and effective therapeutic options for long-term treatment and disease maintenance. Here, we applied a computational approach to discover new drug therapies for IBD in silico, using publicly available molecular data reporting gene expression in IBD samples and 164 small-molecule drug compounds. Among the top compounds predicted to be therapeutic for IBD by our approach were prednisolone, a corticosteroid used to treat IBD, and topiramate, an anticonvulsant drug not previously described to have efficacy for IBD or any related disorders of inflammation or the gastrointestinal tract. Using a trinitrobenzenesulfonic acid (TNBS)-induced rodent model of IBD, we experimentally validated our topiramate prediction in vivo. Oral administration of topiramate significantly reduced gross pathological signs and microscopic damage in primary affected colon tissue in the TNBS-induced rodent model of IBD. These findings suggest that topiramate might serve as a therapeutic option for IBD in humans and support the use of public molecular data and computational approaches to discover new therapeutic options for disease.
- Subjects :
- Fructose therapeutic use
Humans
Inflammatory Bowel Diseases genetics
Inflammatory Bowel Diseases metabolism
Reverse Transcriptase Polymerase Chain Reaction
Topiramate
Anticonvulsants therapeutic use
Computational Biology methods
Fructose analogs & derivatives
Inflammatory Bowel Diseases drug therapy
Subjects
Details
- Language :
- English
- ISSN :
- 1946-6242
- Volume :
- 3
- Issue :
- 96
- Database :
- MEDLINE
- Journal :
- Science translational medicine
- Publication Type :
- Academic Journal
- Accession number :
- 21849664
- Full Text :
- https://doi.org/10.1126/scitranslmed.3002648