“IBD usually develops in young people and can cause severe symptoms that disrupt education, relationships, family life and employment. Better treatments are urgently needed. 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.”
-James Lee, Group Leader of the Crick Research
Researchers from the Francis Crick Institute with the collective teamwork of UCL and Imperial College London, have discovered the key pathway that progresses to inflammatory bowel disease (IBD). Currently 1 in 10 people suffer from IBD, making it affect 5% of the globally estimated population. These diseases that are under the category of IBD are starting to become increasingly common.
The prevalence only makes the situation worse as treatments are not compatible with each and every patient. Attempts to develop newer drugs are futile due to lack of knowledge of the causative factors of IBD. The research that is now published in Nature, elaborated on a gene desert-one that lacks the coding for proteins. This gene does have an ‘enhancer’, that acts as a button for increasing the number of proteins that the genes can produce. This enhancer was present inclusively in active macrophages. This immune cell, which facilitates the gene ETS2, has higher levels of this gene correlated to higher risk of IBD.
The researchers utilised gene editing, indicated that ETS2 was crucial for the inflammatory role played out by macrophages, and that it contributes to the tissue injury in IBD. By increasing the ETS2 amounts, the resting macrophages turned them to inflammatory cells that closely resembles IBD patients. They realised that other genes that are connected to IBD, are also a component of the ETS2 pathway, proving the evidence that it is a major cause of IBD.
Live medications against ETS2 are not present. The team looked for drugs that indirectly decreased its activity. MEK inhibitors, an option for other inflammatory conditions, were anticipated to turn off the inflammatory effects of ETS2. On examining the drug mechanism, they discovered that it can reduce inflammation in macrophages as well as gut samples in IBD patients as well. MEK inhibitors have side effects on other organs, the researchers are working with LifeArc to discover paths that could provide MEK inhibitors directly to macrophages. NIHR BioResource participants voluntarily gave blood samples whether they were affected by IBD or not, and the collaborative work was all across the UK and Europe.
Nivea Vaz
Manipal College of Medical Sciences, Pokhara
Scriveners Online© 