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
Crohn’s disease is a type of inflammatory bowel disease (IBD) that causes chronic inflammation
of 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 experiences.
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.
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
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
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.
an urgent need to defecate
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
Also, a doctor might recommend changing the diet to help reduce symptoms, replace lost
nutrients, and help the gastrointestinal tract heal.
The scientists suspect that if there was a way to block Fn14 using medication, it could make a
A huge difference in the impact that Crohn’s disease has on the human body.
Such a pharmacological 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 is 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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