Treatment and Prevention of Inflammatory Bowel Disease (IBD) using Mutant and Chimeric IL-13 Molecules


Ulcerative colitis (UC) is a chronic inflammatory disease of the colorectum and 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. 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 (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.

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 Natural Killer T (NKT) cells, rather than conventional CD4+T cells, mediate oxazolone colitis and are the source of IL-13 as well as being activated by CD1- expressing intestinal epithelial cells. Tissue removed from ulcerative colitis 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. Building on their previous work, scientists at NIAID and FDA have shown that an Il-13 chimeric fusion protein linked to an effector molecule was able to prevent colitis in a mouse model of ulcerative colitis.

Available for licensing are methods for treating or preventing the inflammatory response of IBD by inhibiting the binding of IL-13 to IL-13 receptors on NKT cells. Additionally, these mutant and chimeric Il-13 molecules are able to block the chronic inflammatory response that results in fibrosis as seen in Crohn's disease. Preventing the inflammatory response of colitis by either modulating or blocking IL-13 and NKT cell activity continues to be an effective therapeutic approach in animal models of colitis with implications for the treatment of human ulcerative colitis and for the treatment of fibrosis associated with Crohn's disease.

Related Invention(s):



Inventors:

Atsushi Kitani (NIAID)  ➽ more inventions...

Stefan Fichtner-Feigl (NIAID)  ➽ more inventions...

Warren Strober (NIAID)  ➽ more inventions...

Ivan Fuss (NIAID)  ➽ more inventions...

Koji Kawakami (FDA)  ➽ more inventions...

Raj Puri (FDA)  ➽ more inventions...

Jan Preiss (NIAID)  ➽ more inventions...

Peter Mannon (NIAID)  ➽ more inventions...


Intellectual Property:
U.S. Pat: 9,072,716 issued 2015-07-07
US Application No. 11/918,711
PCT Application No. PCT/US2006/014393

Publications:
Heller F, et al. PMID 12433369
Fuss IJ, et al. PMID 15146247

Licensing Contact:
Charles Rainwater,
Email: crainwater@niaid.nih.gov
Phone: 301-496-2644

OTT Reference No: E-003-2005/0
Updated: Jul 31, 2012