New research from doctors at the Royal Free Hospital has shown that a ‘boosted’ gene could be a major cause of inflammatory bowel disease (IBD), leading to hopes of more effective treatments being developed.

IBD is the umbrella term for two diseases of the intestinal tract – Crohn’s disease and ulcerative colitis, with over half a million people living with one of these debilitating conditions in the UK.

Despite increasing prevalence, current treatments do not work in every patient and attempts to develop new drugs often fail due to incomplete understanding of what causes IBD.

In research published in Nature today, scientists at UCL and the Royal Free London found that a section of DNA works by ‘boosting’ another gene called ETS2, increasing the amount of protein it makes.

The section of DNA is only active in a particular type of immune cell, called macrophages, known to be prevalent in the intestine of patients with IBD.

The researchers believe that the boosted ETS2 gene is directly responsible for the inflammation and tissue damage in those patients.

The researchers discovered that some existing drugs, currently used for non-inflammatory conditions, can ‘switch off’ the ETS2 gene, but these have significant side effects, so are not suitable for the long-term treatment required.

Instead, doctors are now looking to develop a new generation of drugs that inhibit the ETS2 gene, without any damaging side effects.   

Lead researcher James Lee, a consultant gastroenterologist at the Royal Free Hospital and UCL and group leader of the Genetic Mechanisms of Disease laboratory at the Francis Crick Institute, said: “IBD usually develops in young people and can cause severe symptoms that disrupt education, relationships, family life and employment. We urgently need better treatments for our patients.

“Currently the drugs that can switch off the ETS2 gene are not safe enough for people to take long term as they have side effects in other organs. We are working to find a way to deliver these inhibitors directly to macrophages as this could switch off disease and spell relief for millions of people worldwide. While this is still early days, we believe this is an important discovery and a huge step forward.”

This research was funded by Crohn’s and Colitis UK, the Wellcome Trust, MRC and Cancer Research UK. The researchers also worked with the National Institute of Health Research BioResource and collaborators across the UK and Europe.

Image: James Lee