doctor holding 2d model of stomach and large intestine
Sean Cate
Sean Cate
June 13, 2024 ·  4 min read

A Major Cause of Inflammatory Bowel Disease (IBD) Has Been Discovered

Inflammatory Bowel Disease (IBD) affects millions around the world, including about half a million people in the UK alone. Recent research has shed new light on the genetic mechanisms driving IBD, particularly Crohn’s disease and ulcerative colitis. Scientists from the Francis Crick Institute, University College London, and Imperial College London have identified a crucial genetic factor that could revolutionize the understanding and treatment of these chronic conditions.

Unveiling the Genetic Culprit

DNA Helix
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The key discovery involves a specific section of DNA active in macrophages, a type of immune cell heavily implicated in IBD. This DNA segment, identified as an enhancer, amplifies the expression of a gene called ETS2. ETS2 controls the production of inflammatory chemicals by macrophages, and higher levels of ETS2 are strongly linked to increased inflammation in the gut.1

Dr. James Lee from the Francis Crick Institute elaborated, “This is undoubtedly one of the central pathways that goes wrong for people to get inflammatory bowel disease. It is the process by which one of the most important cells that cause inflammatory bowel disease goes wrong”.2 This enhancer acts as a “master regulator,” triggering excessive inflammatory responses in the intestines, which is a staple of IBD.

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Implications of the Discovery

Doctor holding test tube
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This discovery not only provides a deeper understanding of IBD but also opens up new avenues for treatment. Current treatments for IBD often fail because they don’t address the underlying genetic causes. By targeting the ETS2 pathway, researchers hope to develop more effective therapies that directly mitigate the excessive inflammatory responses characteristic of IBD.3

Dr. James Lee emphasized the potential of this research: “Using genetics as a starting point, we’ve uncovered a pathway that appears to play a major role in IBD and other inflammatory diseases. Excitingly, we’ve shown that this can be targeted therapeutically, and we’re now working on how to ensure this approach is safe and effective for treating people in the future”.

Potential Treatments on the Horizon

scientific testing
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Interestingly, the research team discovered that drugs already approved for other conditions, such as MEK inhibitors used in cancer treatment, could potentially inhibit ETS2 as well. Laboratory experiments have shown that these drugs reduce inflammation in macrophages and gut samples from IBD patients.

However, there are significant challenges ahead. MEK inhibitors can cause serious side effects if not precisely targeted. The next phase of research aims to develop methods to deliver these drugs specifically to macrophages in the gut, minimizing systemic side effects.

Real-World Impact

Woman with stomach pain causes of abdominal pain include inflammatory bowel disease-IBD. stomach ulcer irritable bowel syndrome (IBS), ulcerative colitis and microvilli. closeup photo, blurred.
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For patients like Lauren Golightly, who was diagnosed with Crohn’s disease at the age of 21, this research brings hope. Lauren’s journey with IBD has been fraught with pain and numerous surgeries, including the need for a stoma (an opening in her abdomen to leet waste out). She expresses cautious optimism: “Learning about this research is so exciting and encouraging. I am hopeful this could potentially make a difference for myself and so many other hundreds of thousands of people living with IBD“.

The potential for a targeted treatment that could reduce inflammation without severe side effects represents a significant step forward. Ruth Wakeman, Director of Services, Advocacy and Evidence at Crohn’s & Colitis UK, highlighted the importance of this research: “The more we can understand about Inflammatory Bowel Disease, the more likely we are to be able to help patients live well with these conditions. This research is a really exciting step towards the possibility of a world free from Crohn’s and Colitis one day”.

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Broader Implications for Autoimmune Diseases

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This breakthrough is not just a leap forward for IBD treatment but could also impact other autoimmune diseases. The ETS2 pathway’s involvement in inflammation suggests that similar genetic mechanisms might be at play in conditions like rheumatoid arthritis and lupus.

By understanding the genetic origins of these diseases, researchers can develop more precise and effective treatments, potentially transforming the lives of millions suffering from chronic autoimmune conditions.

Conclusion

Happy patient in hospital
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The discovery of the ETS2 pathway’s role in IBD marks a significant milestone in the quest to understand and treat this debilitating disease. While the path to a new treatment is still in its early stages, the potential benefits for patients are immense. Continued research and clinical trials will be crucial in turning this scientific breakthrough into a practical, life-changing therapy for those living with IBD.

As Dr. James Lee and his team continue their work, the hope for a future where IBD can be effectively managed, or even cured, becomes increasingly tangible. This research not only brings new hope to patients but also exemplifies the profound impact of genetic research in understanding and combating complex diseases.

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Sources

  1. Major cause of Inflammatory Bowel Disease discovered.” Crohns and Colitis. June 6, 2024.
  2. Major cause of inflammatory bowel disease found.” BBC. James Gallagher. June 2024.
  3. Major cause of inflammatory bowel disease discovered.” Science Daily. June 5, 2024.