Scientists discover possible important cause of inflammatory bowel disease

Researchers in the UK appear to have discovered a fundamental genetic cause of inflammatory bowel disease. In a new study Wednesday, the team found evidence of a specific genetic defect that appears to play a key role in prompting immune cells to attack the intestines of people with IBD – a defect found in almost all of the cases they studied. According to the authors, this discovery could lead to the repurposing of new and existing treatments for IBD.

Inflammatory bowel disease is a debilitating and complex disease. state of digestion. The two main types of IBD are known as ulcerative colitis and Crohn’s disease, both of which are characterized by dangerous inflammation of the digestive tract. Symptoms tend to come and go in flare-ups and include abdominal pain, fatigue, diarrhea, rectal bleeding and weight loss.

The main cause of IBD is immune system dysfunction, which chronically damages the intestines. But exact reasons Why this happens is still unclear and may vary from person to person. However, genetics are thought to be an important factor as IBD can run in families.

The new study was carried out by scientists from the Francis Crick Institute, as well as University College London and Imperial College London. They took a closer look at a specific region of our genetic code that has previously been linked to inflammatory bowel disease and autoimmune disorders. This region is one of many in our genome known as a genetic desert, filled with genes that don’t actually code for any proteins. We thought that these deserts contained nothing more than “junk” DNA, but now we know that they can have a significant impact on other, more clearly functional deserts. , genes.

In this wilderness, the team identified a stretch of DNA important for macrophages, immune cells that normally protect us from germs but can also cause the inflammation found in patients with inflammatory bowel disease. The piece of DNA is known as an enhancer and appears to directly influence the activity of a gene called STD2.

The team’s gene-editing experiments found evidence that ETS2 is critical to macrophages’ ability to cause inflammation, including the bad kind that causes inflammatory bowel disease. They also found that tuning ETS2 to be more active could make macrophages in the lab similar to those seen in patients with inflammatory bowel disease. . And when they looked at the genetic makeup of IBD patients, they found that 95% of the patients in their sample had at least one copy of a particular enhancer variant that appears to drive ETS2 activity. The team’s conclusions were published Wednesday in Nature.

“Using genetics as a starting point, we discovered a pathway that appears to play an important role in inflammatory bowel disease and other inflammatory diseases. “said the study’s lead author, James Lee, group leader of the Laboratory of Genetic Mechanisms of Disease at Crick, in statement from high school.

More research will be needed to confirm and better understand how important this variant and the ETS2 gene are in the development of IBD. But given how common the disease is among people with the condition, the team’s work may signal a key step forward for IBD. care. Ongoing medications and lifestyle management based on known triggers can help many, but about half of patients do not respond to initial treatment, and even fewer patients experience long-term remission.

There are currently no drugs specifically designed to combat STD 2. But the team found evidence in laboratory macrophages and intestinal cells taken directly from patients that an existing class of autoimmune drugs known as MEK inhibitors should be able to reduce inflammation. caused by ETS2. The team now plans to develop a way to deliver these drugs directly to macrophages, which should hopefully reduce their known downside. -consequences. With luck, clinical trials on real patients could be carried out within the next five years.

“This research is a truly exciting step towards the possibility of one day ridding the world of Crohn’s disease and colitis,” said Ruth Wakeman. director of services, advocacy and evidence at Crohn’s & Colitis UK, the charity that helped fund the team’s work, the institute said in a statement.