A New Potential Path to Curing Inflammatory Bowel Diseases Emerges through Gene Research Funded by the Crohn's & Colitis Foundation of America

NEW YORK--(BUSINESS WIRE)--Sep 5, 2008 - In the September 5 issue of the journal Cell, a group of researchers led by Richard Blumberg, MD, Chief of the Division of Gastroenterology, Hepatology and Endoscopy at the Brigham and Women's Hospital and Professor of Medicine at Harvard Medical School, together with co-senior investigator Laurie Glimcher, MD, Irene Heinz Given Professor of Immunology and Medicine at Harvard School of Public Health and Harvard Medical School, reported on their discovery of a new genetic risk factor for development of Crohn's disease and ulcerative colitis - collectively known as inflammatory bowel diseases (IBD). The research team developed an experimental mouse to test the role of a gene called XBP1 as a risk factor for these currently incurable digestive diseases affecting millions of people around the world. In the mouse model, they deleted the XBP1 gene within the epithelium--those cells that line the intestine. The epithelium is the front line for immunologic response to the billions of bacteria that reside in the intestine. The experimental mice with the missing gene spontaneously developed an intestinal inflammation that resembled IBD. The study demonstrated how the lack of the XBP1 gene disabled the normal communication between intestinal epithelial cells and gut bacteria, resulting in dysfunctional immune response and disease.

It has long been speculated that epithelial cells play a critical role in the development of Crohn's disease and ulcerative colitis. These cells are strategically based between the largest concentrations of bacteria and immune cells in the human body--the intestine. This study provides direct evidence that epithelial cells are directly involved in initiating disease through genetic alterations. Arthur Kaser, MD, Ann-Hwee Lee, PhD, and colleagues at the Brigham and Women's Hospital and Harvard Medical School in Boston collaborated with scientists in Germany, the Netherlands, and Austria to demonstrate that alterations in the gene in the intestinal lining cells represent risk factors for development of both major forms of IBD, Crohn's and colitis. Dr. Blumberg commented: "These exciting studies elucidate a novel pathway that underlies the development of IBD. Combined with the new mouse model, we have a unique means to develop new classes of therapeutics to treat both Crohn's disease and ulcerative colitis."

The Crohn's & Colitis Foundation of America (CCFA) offers grants to researchers through an RFP process in order to accelerate research into cures for these intractable digestive diseases. With the development of genome science, there are now over thirty genes pinpointed as risk factors for Crohn's and colitis. R. Balfour Sartor, MD, Chief Medical Advisor for CCFA commented, "We at the Crohn's & Colitis Foundation are very encouraged by the example set by Dr. Blumberg and his colleagues. By initiating a basic research study through a CCFA grant, they were able to identify a genetic pathway and then expand the research to an international clinical study involving nearly 5,000 IBD patients and controls. We are hopeful their findings will contribute to the development of future therapeutics to benefit patients around the world."

Additional funding for expanded research came from National Institutes of Health, the Ellison Medical Foundation, the DFG/German Ministry of Science Excellence Cluster, the Austrian Science Fund and the Max Kade Foundation. Listen to a podcast of Drs. Blumberg and Glimcher discussing this research on http://www.cell.com.

About the Crohn's & Colitis Foundation of America

The Crohn's & Colitis Foundation of America's mission is to cure Crohn's disease and ulcerative colitis, and to improve the quality of life of children and adults affected by these diseases. The Foundation ranks third among leading health non-profits in the percentage of expense devoted to research toward a cure, with more than 81 cents of every dollar the Foundation spends goes to mission-critical programs. The Foundation consistently meets the standards of organizations that monitor charities, including the Better Business Bureau's Wise Giving Alliance (give.org) and the American Institute of Philanthropy (charitywatch.org). For more information, contact the Foundation at 800-932-2423 or visit www.ccfa.org.

Contact

The Crohn's & Colitis Foundation of America
Ariella Levine, 646-943-7430
alevine@ccfa.org

 

Posted: September 2008

View comments

Hide
(web4)