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.
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.
- 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."
Dr. Fabio Cominelli