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reatment options for Crohn's disease
tend to focus on symptom control, but new research highlights a potential
treatment option that targets a pathway in the immune system itself.
Scientists zoom in on an immune pathway that may help treat Crohn's.
Scientists
at Case Western Reserve University School of Medicine in Cleveland, OH, have
published the results of their 3 year study in the journal Cellular and Molecular
Gastroenterology and Hepatology.
Crohn's disease is a type of
inflammatory bowel disease (IBD) that causes chronic inflammationof the
gastrointestinal tract.
Current
treatment options help alleviate symptoms and manage remission, but scientists
are still researching targeted treatment.
The
new study focused on just that. It investigated the chronic inflammation that
people genetically prone to Crohn's disease often experience.
Dr.
Fabio Cominelli, chief of gastroenterology at University Hospitals Cleveland
Medical Center, led the study.
A
type of protein called tumor necrosis factor
— or tumor necrosis factor-like weak inducer of apoptosis (TWEAK) — interacts
with receptors called Fn14 on the surface of the intestine.
This
study used mouse models to look at the interaction between the two. The
researchers were interested to see if this interplay has a role in protecting
the intestine, and whether or not it was also able to trigger inflammation.
Research showed promise for humans
For
the study, the researchers used genetically engineered mice with a Crohn's-like
condition. The researchers deleted Fn14 receptors in these mice.
Those
without receptors experienced less severe inflammation, while those with Fn14
receptors had chronic, ongoing inflammation. The latter group also experienced
scarring.
"During
early inflammation, TWEAK/Fn14 activates to heal tissue damage," explains
Dr. Cominelli. "However, during later, chronic inflammation, increased and
persistent levels of Fn14 may lead to pathologic inflammation and
fibrosis."
Although
this was an important finding, the results may not have necessarily translated
to humans.
So,
Dr. Cominelli and team set out to use molecular diagnostics to examine
intestinal tissue from people with and without IBD.
They
found that the interaction between TWEAK and Fn14 was overexpressed in people
with Crohn's.
Crohn's disease basics
In
the United States, IBD affects around 3 million people. Crohn's disease, which is one
type of IBD, can affect any part of the gastrointestinal tract but most
commonly affects the end of the small bowel and beginning of the colon.
Although
the condition can affect everyone differently, there are some signs and
symptoms that many people experience.
These include:
·
ongoing diarrhea
·
rectal bleeding
·
an urgent need to defecate
·
abdominal cramps
·
abdominal pain
·
a feeling of incomplete bowel
evacuation
There
are also potential complications, including appetite loss, weight loss, low
energy, and fatigue.
In severe cases, complications may include fissures, fistulas, and strictures,
all of which can be painful and, in some cases, dangerous.
Treatment includes medications that suppress the immune
system so it stops causing inflammation.
Also,
a doctor might recommend changing the diet to help reduce symptoms, replace
lost nutrients, and help the gastrointestinal tract heal.
Future applications of this research
The
scientists suspect that if there was a way to block Fn14 using medication, it
could make a huge difference in the impact that Crohn's disease has on the
human body.
Such
a pharmcological intervention could improve inflammation and reduce the
scarring that often accompanies the condition.
Also,
there may be implications for colorectal cancer; those who have IBD and
experience chronic inflammation are at greater risk of developing colorectal cancer.
If
this potential treatment alleviates inflammation and scarring, it could also
reduce a person's risk of this type of cancer.
"This research establishes the
rationale for investigating innovative therapies that can improve and save
lives."
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