Major Breakthrough in Inflammatory Bowel Disease Research Offers New Hope

 Researchers have identified a key driver of inflammatory bowel disease (IBD) and other immune disorders affecting the spine, liver, and arteries, sparking hope for millions worldwide.

The discovery is particularly promising because it reveals a biological pathway that can be targeted with existing drugs. Efforts are already underway to adapt these medications for IBD and related conditions.

Dr. James Lee, the group leader of the Genetic Mechanisms of Disease Laboratory at the Francis Crick Institute in London, hailed the discovery as significant. “We’ve uncovered one of the central pathways that malfunction in inflammatory bowel disease, which has been a major research goal,” he said. “This finding is not only crucial for fundamental immunology but also provides a treatable target.”

Over half a million people in the UK and at least 7 million globally suffer from IBD, including Crohn’s disease and ulcerative colitis. These conditions arise when the immune system attacks the bowel, causing symptoms such as abdominal pain, weight loss, diarrhea, and blood in stools. While medications like steroids can alleviate symptoms, some patients require surgery to remove affected parts of the bowel.

Lee’s team discovered this breakthrough while investigating a “gene desert” on chromosome 21, a DNA stretch previously linked to IBD and other autoimmune diseases. Published in Nature, their research describes how they found a DNA section acting as a volume control for nearby genes. This "enhancer" was identified in immune cells called macrophages, where it boosted a gene named ETS2, increasing the risk of IBD.

Gene editing experiments confirmed that ETS2 is central to the inflammatory behavior of macrophages, contributing to bowel damage in IBD. “The search for central drivers of this pathogenic process has led us to this discovery,” said Lee, who is also a consultant gastroenterologist at the Royal Free Hospital and UCL.

This biological pathway is also believed to drive other autoimmune disorders, including ankylosing spondylitis, which causes spine and joint inflammation, and rarer autoimmune diseases affecting the liver and arteries.

While no drugs specifically target the ETS2 gene, the researchers identified a class of anticancer drugs called MEK inhibitors that could potentially reduce the gene’s activity. In lab tests, these drugs reduced inflammation in gut samples from IBD patients.

To minimize side effects on other organs, the team is adapting the medicine to target only macrophages. They are creating a “conjugate” that attaches the drug molecule to a synthetic antibody binding solely to target cells. “This approach is safer because it’s more targeted, allowing for lower doses,” said Lee. “We have already developed the antibody conjugate, which is ready for testing.”

Clinical trials are needed to determine if the adapted drug can reduce IBD and other autoimmune conditions. However, since MEK inhibitors are already used in cancer treatment, researchers hope the approval process could be expedited, possibly within five years.

Further research showed that the ETS2 gene is at least half a million years old, carried by Neanderthals and other archaic humans. “Its preservation throughout evolutionary history suggests its importance in early bacterial responses,” Lee explained. “We don’t want to eliminate it entirely, just reduce its activity by 50%, which may suffice.”

Ruth Wakeman from Crohn’s and Colitis UK commented, “Crohn’s and colitis are complex, lifelong conditions without a cure. Research like this is helping us answer critical questions about their causes. This discovery is a significant step towards a future without Crohn’s and colitis.”