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Immune factor GM-CSF significantly
improves Crohn's disease symptoms
Findings support new theory of mechanism
behind inflammatory disorder
BOSTON - May 25, 2005 - A drug that stimulates a specific
part of the immune system may improve symptoms of Crohn's disease,
according to a study in the May 26 New England Journal of Medicine.
A multi-institutional research team reports that treatment with
the growth factor GM-CSF significantly reduced symptom severity
and improved quality of life after 56 days of daily drug injections.
The finding supports a new concept that Crohn's, rather than being
caused primarily by an excessive immune response, could actually
result from defects in the body's first line of immune defense.
"We've proposed that the inflammation that occurs with Crohn's
is actually secondary to an earlier problem," says Joshua Korzenik,
MD, co-director of the Crohn's and Colitis Center at Massachusetts
General Hospital (MGH), lead author of the NEJM study. "We
believe there is a defect with the gastrointestinal innate immune
system, a group of cells that stop any microbes from entering the
body. If normal intestinal bacteria are not controlled by the innate
immune system, a compensatory secondary inflammation could produce
the symptoms of Crohn's."
Korzenik has been investigating this hypothesis for several years,
in collaboration with Brian Dieckgraefe, MD, PhD, of the Gastroenterology
Division at Washington
University School of Medicine in St. Louis, a co-author of the
current study.
A chronic inflammatory bowel disease, Crohn's usually affects the
small intestine, causing abdominal pain and chronic diarrhea. Serious
symptoms can include ulceration, bleeding, the development of fistulas
- openings from affected areas into other organs - or intestinal
blockage. About half a million people in the U.S.are affected by
Crohn's. Current treatments are designed to reduce symptoms, and
the disorder often enters periods of remission, some lengthy, before
recurring.
Korzenik and Dieckgraefe developed their hypothesis based on studies
of certain genetic disorders known to affect the innate immune system.
Because some of these disorders include symptoms virtually identical
to those of Crohn's, they wondered if a similar process was occurring
in Crohn's patients, with the excessive inflammatory response actually
resulting from an unsuspected defect in innate immunity. To test
this concept, they conducted a pilot study of treatment with GM-CSF,
which stimulates the innate immune system and is usually used to
restore bone marrow function in chemotherapy patients. Promising
results from that study, published in 2002, led to the current multicenter
investigation.
Patients with moderate to severe Crohn's disease enrolled in the
study at 28 centers across the U.S. Of the 94 participants who completed
the 56-day treatment cycle, 57 received daily injections of GM-CSF,
while 37 received placebo injections. Participants were evaluated
every two weeks during the study period and 30 days after treatment
concluded. Based on a standard index of Crohn's disease symptoms,
significantly more participants receiving GM-CSF were judged to
have major improvement or remission of their symptoms than were
those receiving placebo injections.
"We're encouraged that these results support this new understanding
of Crohn's and hope they will lead to a new treatment option for
the disease," says Korzenik, an assistant professor of Medicine
at Harvard Medical School. "We're working with other institutions
to conduct the larger-scale studies that would be needed to apply
for FDA approval for this use of GM-CSF.
The study was supported by a grant from Berlex, Inc. which manufactures
Leukine (sargramostim), the recombinant form of GM-CSF used in this
research. The report's additional co-authors are John Valentine,
MD, of the University of Florida, and Diana Hausman, MD, and Mark
Gilbert, MD, of Berlex.
Massachusetts General Hospital, established in 1811, is the original
and largest teaching hospital of Harvard Medical School. The MGH
conducts the largest hospital-based research program in the United
States, with an annual research budget of more than $450 million
and major research centers in AIDS, cardiovascular research, cancer,
cutaneous biology, medical imaging, neurodegenerative disorders,
transplantation biology and photomedicine. In 1994, MGH and Brigham
and Women's Hospital joined to form Partners HealthCare System,
an integrated health care delivery system comprising the two academic
medical centers, specialty and community hospitals, a network of
physician groups, and nonacute and home health services.
Media Contact: Sue
McGreevey, MGH Public Affairs
Physician Referral Service: 1-800-388-4644
Information about Clinical Trials
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