A Method of Treating Inflammatory Bowel Disease (IBD)
Description of Invention:
Ulcerative colitis (UC) is a chronic inflammatory disease of the colorectum and affects approximately 400,000 people in the United States (of these, approximately 5% develop colon cancer). The cause of UC is not known, although an abnormal mucosal T cell, responsive to bacterial antigens in the gut microflora, is thought to be involved. Present treatments for UC include anti-inflammatory therapy using aminosalicylates or corticosteroids, as well as immunomodulators and diet. However, 25-40% of ulcerative colitis patients must eventually have their colons removed due to massive bleeding, severe illness, rupture of the colon, risk of cancer or due to side effects of corticosteroids and novel treatments are still actively being sought. NIH scientists and their collaborators have used a mouse model of experimental 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 (Immunity (2002) 17, 629-638).
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 and that NKT cells 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 and that in keeping with epithelial damage being a key factor in UC, these NKT cells are cytotoxic for epithelial cells (J Clin.Investigation (2004) 113, 1490-1497).
With obvious implications for the treatment of human Ulcerative Colitis, inflammation in this mouse model has been shown to be effectively blocked by neutralizing IL-13 or by inhibiting the activation of NK-T cells through CD1. Available for licensing are broad claims covering treatments preventing the inflammatory response of colitis by modulating IL-13 and NKT cell activity and methods for screening for therapeutic compounds effective for colitis.
Inventors:
Warren Strober (NIAID) Ivan Fuss (NIAID) Frank Heller (NIAID) et al.
Patent Status:
DHHS Reference No. E-131-2002/0 --
PCT Application No. PCT/US2002/018790 filed 14 Jun 2002, which published as International Publication No. WO 2004/001655 on 31 Dec 2003
U.S. Patent Application No. 10/517,898 filed 13 Dec 2004
Licensing Status: In addition to licensing, the technology is available for further development through collaborative research with the inventors via a Cooperative Research and Development Agreement (CRADA).
