Treatment of Inflammatory Bowel Disease (IBD) Using IL-13 Modulators and Inhibitors
Posted Oct 11 2010 8:00pm
Description of Invention: Ulcerative colitis (UC), a chronic inflammatory disease of the colorectum, affects approximately 400,000 people in the United States. The cause of UC is not known, although an abnormal immunological response to bacterial antigens in the gut microflora is thought to be involved. Available for licensing are broad claims covering (1) treatments preventing the inflammatory response of colitis by modulating IL-13 and Natural Killer T cell (NKT) activity and (2) methods for screening for therapeutic compounds effective for colitis. NIH scientists and their collaborators have used a mouse model of experimental colitis (oxazolone colitis, OC) to show that IL-13, a Th2 cytokine, is a significant pathologic factor in OC and that neutralizing IL-13 in these animals effectively prevents colitis. Inflammation in this mouse model has also been shown to be effectively blocked by neutralizing IL-13 or by inhibiting the activation of NK-T cells through CD1.
Oxazolone colitis (OC) is a colitis induced by intrarectal administration of a relatively low dose of the haptenating agent oxazolone subsequent to skin sensitization with oxazolone. A highly reproducible and chronic colonic inflammation is obtained that is histologically similar to human ulcerative colitis. Studies show that NKT cells, rather than conventional CD4+T cells, mediate oxazolone colitis, are the source of IL-13, and are activated by CD1 expressing intestinal epithelial cells. Tissue removed from UC patients were also shown to contain increased numbers of nonclassical NKT cells that produce markedly increased amounts of IL-13. In addition, these NKT cells are cytotoxic for epithelial cells, supporting the concept that epithelial damage is a key factor in UC.
Applications: Development of IL-13 and CD1 based therapeutics to treat or prevent ulcerative colitis.
Development Status: Small animal model studies.
Inventors: Warren Strober (NIAID) Ivan J Fuss (NIAID) Frank Heller [ex-Schieffele] (NIAID)
IJ Fuss et al. Nonclassical CD1d-restricted NK T cells that produce IL-13 characterize an atypical Th2 response in ulcerative colitis. J Clin Invest. 2004 May;113(10):1490-1497. [ PubMed: 15146247 ]
F Heller et al. Oxazolone colitis, a Th2 colitis model resembling ulcerative colitis, is mediated by IL-13-producing NK-T cells. Immunity 2002 Nov;17(5):629-638. [ PubMed: 12433369 ]
Licensing Status: Available for licensing.
Portfolios: Internal Medicine Internal Medicine - Therapeutics Internal Medicine - Other
For Licensing Information Please Contact: Suryanarayana Vepa Ph.D. NIH Office of Technology Transfer 6011 Executive Blvd. Suite 325, Rockville, MD 20852 United States Email: firstname.lastname@example.org Phone: 301-435-5020 Fax: 301-402-0220