This one protein may help physicians treat IBD symptoms.
If you have some form of inflammatory bowel disease (IBD) — the umbrella term for a range of gastrointestinal conditions that include Crohn’s disease and ulcerative colitis (UC) — you’ve most likely experienced uncomfortable inflammation in your day-to-day life.
IBD provides a challenge to doctors in that there is no treatment that works for everyone and the exact cause remains unknown.
Now, new research has identified a protein that is a driver for inflammation.
Published this month in the journal Cell Reports, these findings are significant in that they could lead to better targeted treatments for people with IBD down the line.
In the study, researchers from Sanford Burnham Prebys Medical Discovery Institute (SBP) in La Jolla, California, in collaboration with Technion – Israel Institute of Technology in Haifa, Israel, found that a gene called RNF5 regulates the activity of a protein called S100A8, which causes inflammation.
The researchers came across this by creating a group of lab mice born without RNF5. As a result, these mice showed minimal initial signs of intestinal inflammation.
Then the mice were given a compound that can give your gut inflammation through their drinking water.
Healthy mice would normally just experience minor inflammation if given this agent, but these mice — without the protective RNF5 gene — developed more extreme inflammation, getting a type of colitis. Almost half of these mice died over the course of several weeks.
“This certain level of inflammation caught our attention. When we gave the mice inflammatory agents in their drinking water, those who had a lack of the RNF5 gene had very serious inflammation, diarrhea — basically, all of the characteristics of IBD,” Ze’ev Ronai, PhD, lead author of the study and professor at SBP’s National Cancer Institute-Designated Cancer Center, told Healthline.
“The fact that almost 50 percent of the mice died as a result of this very minor inflammatory agent indicated that this protein is very important in preventing IBD.”
Ronai said the mice without RNF5 had significant amounts of S100A8 — a protein that leads to inflammation — in their intestinal cells. Basically, think of RNF5 as a gatekeeper that keeps an eye out for potentially harmful material that should be disposed of. Without this cellular bouncer guarding the door, these mice were set up for damaging, ultimately deadly, inflammation.
The team also tested their theory in 19 people with ulcerative colitis. They found these patients had higher levels of S100A8 in tissue samples if they had worse symptoms.
Dr. Garrett Lawlor, assistant professor of medicine at the Columbia University Vagelos College of Physicians and Surgeons and associate director of Columbia’s inflammatory bowel program in New York City, wrote in an email to Healthline that this research has potential relevance to people who suffer from IBD.
“If this research translates into human biology, we could potentially target and neutralize this protein as a form of therapy for IBD,” wrote Lawlor, who wasn’t involved in this research.
“This is so important as up to 40 percent of patients do not respond to many of the therapies we currently have available to treat IBD. The more options available to us for therapy, the better we can individualize to hit the right target for each patient’s disease.”
Dr. Jordan Axelrad, MPH, a gastroenterologist at NYU Langone Health, told Healthline that it has been particularly challenging for the medical community to develop treatments for IBD given that it isn’t a “one-hit” condition.
“There isn’t one sole environmental trigger. It’s a complex disease that involves both environmental triggers and a person’s genetic susceptibility and immune response,” Axelrad said.
“It’s very difficult to parse out the specific causes of IBD and find ways to provide proper maintenance of the disease.”
That being said, he added that we are moving toward a better understanding of the condition, and there is a “growing number of promising targets for novel therapeutic approaches.” He said that this research — while still early in its findings — suggests a promising future for developing better therapeutic treatments for IBD.
But for people with IBD reading this now, the new research doesn’t offer any immediate help.
“Right now, this means little for IBD patients, as it can still take a number of years before a promising target can get through laboratory and human trials. This may be a useful therapy that is approved to be safe and effective, and available in 5–10 years,” Lawlor added.
That being said, Lawlor wrote that research like this is “vital to getting a broader understanding of the inflammatory processes that work together to cause IBD.
“It is also possible that with this greater understanding of the disease process, that we may down the road discover a cure,” he added.
For his part, Ronai said that there are a number of directions he and his team could head moving forward. He said that one would be to understand what could be the best agent to fight the inflammation-causing S100A8 protein. They basically are trying to figure out what are the best points on the protein that they could attack.
He also added that this work can have ramifications beyond IBD.
Better understanding the proteins that cause IBD inflammation could have a related effect of better understanding ways to treat cancer.
“We are trying to understand the manifestation of our findings when it comes to cancer and the reason for why the current immunotherapies that are abundantly given to cancer patients — when effective — are also causing inflammatory disorders,” Ronai added.
New research has identified a protein that is a driver for inflammation that could be linked to IBD symptoms.
The study is preliminary, but experts say if further research bolsters these findings, it could help physicians target the root cause of IBD.