Drug-targetable driver of inflammatory bowel disease (IBD) discovered and can be treated with existing drugs

Good news!

"... The new study in Nature identified a gene called ETS2 is essential for inflammatory functions in macrophages – a type of immune cell important in IBD. ...

ETS2 can be blocked using drugs  which are already prescribed for other non-inflammatory conditions, and they result in reduced inflammation. ..."

From the abstract:

"Increasing rates of autoimmune and inflammatory disease present a burgeoning threat to human health. This is compounded by the limited efficacy of available treatments and high failure rates during drug development, highlighting an urgent need to better understand disease mechanisms. Here we show how functional genomics could address this challenge. By investigating an intergenic haplotype on chr21q22—which has been independently linked to inflammatory bowel disease, ankylosing spondylitis, primary sclerosing cholangitis and Takayasu’s arteritis—we identify that the causal gene, ETS2, is a central regulator of human inflammatory macrophages and delineate the shared disease mechanism that amplifies ETS2 expression. Genes regulated by ETS2 were prominently expressed in diseased tissues and more enriched for inflammatory bowel disease GWAS hits than most previously described pathways. Overexpressing ETS2 in resting macrophages reproduced the inflammatory state observed in chr21q22-associated diseases, with upregulation of multiple drug targets, including TNF and IL-23. Using a database of cellular signatures, we identified drugs that might modulate this pathway and validated the potent anti-inflammatory activity of one class of small molecules in vitro and ex vivo. Together, this illustrates the power of functional genomics, applied directly in primary human cells, to identify immune-mediated disease mechanisms and potential therapeutic opportunities."

Drug-targetable driver of IBD discovered Researchers in the UK have discovered a biological pathway that plays a major role in driving inflammatory bowel disease (IBD) and can be targeted using existing drugs.

Major cause of inflammatory bowel disease discovered (original news release) Researchers at the Francis Crick Institute, working with UCL and Imperial College London, have discovered a new biological pathway that is a principal driver of inflammatory bowel disease (IBD) and related conditions, and which can be targeted using existing drugs.

A disease-associated gene desert directs macrophage inflammation through ETS2 (open access)

Fig. 1: Resolving molecular mechanisms at chr21q22. (Is this an example of information overload?)