BREAKING NEWS IN INFLAMATORY DISEASES STUDY

SOURCE: IBDsucks:::: FOR IMMEDIATE RELEASE: Major Genetic Link to Crohn's and Colitis Found Discovery Should Lead to Improved Therapies and Diagnosis

New York, NY – October 26, 2006: A major genetic link to the development of Crohn's disease and ulcerative colitis, as well as other inflammatory diseases, has been revealed in a recent study. "This genetic discovery is special because it may have a rapid impact on diagnosis and treatment of these chronic digestive diseases," said Jonathan Braun, M.D., Ph.D., Chair of the National Scientific Advisory Committee of the Crohn's & Colitis Foundation of America (CCFA). "It is also important news for a spectrum of inflammatory diseases, because the gene may similarly affect patients with psoriasis, rheumatoid arthritis, and multiple sclerosis." The study, announced today in an online publication of the journal Science, builds on a groundwork laid by more than $125 million in Crohn's and colitis research funded by CCFA.

Since the mapping of the human genome, researchers have slowly begun to unravel the genetic components to the development of Crohn's and colitis. These diseases, which affect 1.4 million Americans, are now known to involve variants of a number of different genes. Previous genetic studies uncovered a link between Crohn's and variants of the gene CARD15 (also known as NOD2), but this gene plays a role in only some Crohn's patients, and does not affect the risk for colitis. This new discovery, which involves a gene called the interleukin-23 (IL-23) receptor, has a much larger effect on these inflammatory diseases, and affects risk for both Crohn's and colitis.

"All the evidence we have to date indicates that disease risk for Crohn's and colitis is a mosaic," said Dr. Braun, who is also a professor at the Geffen School of Medicine and Chair of the Department of Pathology & Lab Medicine at the University of California at Los Angeles (UCLA) Medical Center. "Combinations of genes can predispose you to certain outcomes, leaving you susceptible or resistant to different conditions. By identifying these genes and their role in disease biology, we can better predict risk and develop compensatory therapies. In the last few years, basic immunology research, supported in part by CCFA, has helped to uncover a role for IL-23 in the control of inflammation. This new study gives us the genetic evidence that IL-23 is important in human disease."

Dr. Braun also notes that while the disease state of all Crohn's and colitis patients is not likely to be driven by IL-23, the drugs necessary to affect change in the behavior of this protein receptor already exist. In fact, one such therapy was recently reported by a team at the National Institutes of Health (NIH). The investigators were able to show that therapy targeting p40, a subunit of IL-23, can inhibit the activity of IL-23 in Crohn's disease (Mannon P, N Engl J Med 351:2069, 2004). This genetic discovery is likely to accelerate tests of this and other drugs, and to better identify which patients will benefit from such treatments.

Richard H. Duerr, M.D., the study's first author, is the associate professor of medicine and human genetics at the University of Pittsburgh. "We identified genetic variants in the IL-23 receptor gene that confer increased risk for IBD, but we are most excited about our discovery of a genetic factor in the same gene that confers protection against developing IBD," said Dr. Duerr. "We are hopeful that ongoing research will tease out the specific downstream effects of these genetic variants so that this knowledge can be used to develop better, more targeted therapies for patients with IBD." Dr. Duerr has been the recipient of several CCFA research grants, including a research fellowship award and two senior research awards focusing on identifying IBD genes on chromosomes 2, 3, and 12.


The IL-23 study's senior author, Judy H. Cho, M.D., is director of the Inflammatory Bowel Disease Center at Yale University. Her research on the genetics of inflammatory disease was inaugurated with a Career Development Award from CCFA on "Genetic Mapping Studies in IBD," and she was the founding chairperson of CCFA's DNA and Cell Line Bank (precursor of the NIDDK'S Genetics Consortium, which performed the IL-23 study). In 2001, a multi-center team including Dr. Gabriel Nunez (University of Michigan) and Dr. Cho identified the first susceptibility gene for Crohn's disease, CARD15 (NOD2). Five of the six senior investigators of the Genetics Consortium are currently supported by CCFA, including Drs. Stephan Brant (Johns Hopkins University), Richard Duerr (University of Pittsburgh), Kent Taylor (Cedars Sinai Medical Center), and John Rioux (Broad Institute, and now University of Montreal).

CCFA's research efforts are guided by Challenges in IBD Research, a strategic research plan developed by the top minds in the Crohn's and colitis research field. Nearly four decades of research into the immune regulation of the gut have yielded significant advances and led to the development of a number of promising therapies. This new discovery will inform future research into the genetic variants that contribute to the development of inflammatory bowel disease.

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Date Posted: October 26, 2006