Woman using digital x-ray of human intestine holographic scan projection 3D rendering

(© sdecoret - stock.adobe.com)

LONDON — Scientists have made a groundbreaking discovery in the fight against inflammatory bowel disease (IBD). A team in London says a major cause of this painful condition centers around a single gene discovered in the body’s “gene desert.” The new findings could soon lead to a new way of treating the disease.

The findings, in a nutshell:

Researchers at the Francis Crick Institute identified a key player in this condition: the ETS2 gene. This gene, hiding in a previously overlooked “gene desert” in our DNA, acts like a remote control’s volume button for inflammation in our gut. When turned up too high, it causes our immune cells, specifically macrophages, to go into overdrive, leading to the painful symptoms of IBD.

However, scientists say we might already have the tools to turn down this inflammatory dial. The researchers found that drugs called MEK inhibitors, currently used for other conditions, can effectively reduce ETS2’s activity. When tested on gut samples from IBD patients, these drugs showed promising results in reducing inflammation. This discovery is a beacon of hope for the millions worldwide who grapple with autoimmune diseases like IBD.

According to the CDC, roughly 3.1 million adults (1.3%) in the United States have been diagnosed with IBD. This condition is a general term that includes Crohn’s disease and ulcerative colitis.

“IBD usually develops in young people and can cause severe symptoms that disrupt education, relationships, family life and employment. Better treatments are urgently needed,” says James Lee, the group leader at the Genetic Mechanisms of Disease Laboratory at the Crick, in a media release.

“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.”

Man battling stomach pain from possible gastrointestinal disorder
Researchers at the Francis Crick Institute identified a key player in this condition: the ETS2 gene. (© Prostock-studio – stock.adobe.com)

How did researchers make the discovery?

So, how did scientists uncover this hidden culprit in our genes? Their journey, published in the journal Nature, began in this “gene desert” – a vast stretch of DNA that doesn’t code for proteins. Think of our DNA as a giant library. Some books (genes) give direct instructions for making proteins, while others (gene deserts) seem empty but can secretly hold crucial information.

In this seemingly barren area, the team found an “enhancer.” If genes are like light bulbs, enhancers are the dimmer switches that control their brightness. This particular enhancer was cranking up the ETS2 gene, but only in one type of immune cell: macrophages. These cells are like the body’s cleanup crew, usually maintaining order in our gut. However, when ETS2 is overactive, it transforms into inflammatory troublemakers.

To understand ETS2’s role, the scientists used genetic editing – think of it as carefully rewriting parts of the cell’s instruction manual. They found that without ETS2, macrophages couldn’t perform their inflammatory functions. Even more tellingly, simply increasing ETS2 in normal macrophages turned them into inflammatory cells that looked just like those in IBD patients.

The team also discovered that many other genes previously linked to IBD are part of the ETS2 pathway. It’s like finding out that multiple suspects in a crime are all part of the same gang, solidifying ETS2’s role as a ringleader in IBD.

The final step was finding a way to counteract ETS2. The researchers scoured through existing drugs and hit upon MEK inhibitors. These drugs, already used for non-inflammatory conditions, were predicted to switch off ETS2’s inflammatory effects. Testing this hypothesis on real gut samples from IBD patients, they saw a significant reduction in inflammation.

This research represents a major leap forward in understanding and potentially treating IBD. By unraveling the complex genetic factors behind this condition, scientists have opened up new avenues for treatment, offering hope to those whose lives are disrupted by this debilitating disease.

“IBD and other autoimmune conditions are really complex, with multiple genetic and environmental risk factors, so to find one of the central pathways, and show how this can be switched off with an existing drug, is a massive step forwards,” says study first author Christina Stankey, a PhD student at the Crick.

What does an IBD patient go through?

Lauren Golightly was only in her early 20s when doctors diagnosed her with Crohn’s Disease in 2018. Golightly was experiencing stomach cramps, blood in her stool, and irregular bowel habits before going for a checkup.

“Crohn’s has had a huge impact on my life. I’ve had a rocky road since diagnosis, with many hospital admissions, several different medications and even surgery to have a temporary stoma bag. One of the hardest things about having Inflammatory Bowel Disease (IBD) is the uncertainty around it. I still experience flare-ups and can still spend quite a bit of time in hospital. 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,” says Golightly, now 27 years-old.

The research team received funding from Crohn’s and Colitis UK, the Wellcome Trust, MRC, and Cancer Research UK.

About Chris Melore

Chris Melore has been a writer, researcher, editor, and producer in the New York-area since 2006. He won a local Emmy award for his work in sports television in 2011.

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