Scientists pinpoint driver of IBD and other disorders; work under way to adapt existing drugs

From the article:

Lee’s research team “stumbled” on the discovery after investigating a “gene desert”, a stretch of DNA on chromosome 21 that does not code for proteins, which has previously been linked to IBD and other autoimmune diseases. Writing in Nature, they describe how they found a section of DNA that behaves like a volume control for nearby genes. This “enhancer” was seen only in immune cells called macrophages where it boosted a gene called ETS2 and ramped up the risk of IBD.

Through gene editing experiments, the scientists showed that ETS2 is central to the inflammatory behaviour of macrophages and their ability to damage the bowel in IBD. “There’s been a search for some time for the central drivers of this pathogenic process, and this is what we’ve stumbled on,” said Lee, who is also a consultant gastroenterologist at the Royal Free hospital and UCL.

The same biological pathway is thought to drive other autoimmune disorders, including ankylosing spondylitis, which causes spine and joint inflammation in about one in 1,000 people worldwide, and rarer autoimmune diseases that affect the liver and arteries.

While there are no drugs that specifically target the ETS2 gene, the scientists identified a class of anticancer drugs called MEK inhibitors that they suspected would dampen the gene’s activity. In laboratory tests, the drugs performed as expected, reducing inflammation in gut samples from patients with IBD.