A New Potential Path to Curing Inflammatory Bowel Diseases Emerges through Gene Research...

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

Harvard Medical School based investigators and international team
pinpoint the role of the XBP1 gene in the development of Crohn's and
colitis, digestive diseases affecting over 1.4 Million people in the
US alone
NEW YORK--(Business Wire)--
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.

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

Copyright Business Wire 2008