Will a new target pathway for IBD lead to better treatments?
Although the prevalence of IBD has increased every year, with approximately one in 100 people in the U.S. having a form of inflammatory bowel disease, current treatments are not effective for every patient. Researchers at the Francis Crick Institute, University College London, and Imperial College London have identified a new biological pathway critical in driving inflammatory bowel disease (IBD) and other related conditions such as Crohn's disease and ulcerative colitis.
The researchers began by exploring a 'gene desert'—a region of DNA that does not code for proteins—which was previously linked to IBD and other autoimmune diseases. In this region, they found an 'enhancer' gene, a short piece of DNA that can increase the protein production of nearby genes. This enhancer gene was found to boost protein production only in macrophages (a type of immune cell), where it boosted a gene called ETS2.
Scientists found that increasing the amount of ETS2 genes in macrophages turned the macrophages into inflammatory cells, resembling those from IBD patients. Researchers also found that other genes previously associated with IBD are part of the ETS2 gene pathway.
The discovery of the ETS2 pathway is significant because it allows for the exploration of potential treatments with existing drugs. Although there are no drugs that block ETS2, there are drugs that reduce its activity. Researchers discovered that MEK inhibitors, existing drugs for non-inflammatory conditions, reduce ETS2's inflammatory effects. During testing, the MEK inhibitors were shown to reduce inflammation in macrophages as well as in gut samples from patients with IBD. Currently, the researchers are working on methods to deliver these drugs directly to macrophages to minimize systemic side effects on the body.
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