Endometriosis-associated gene identified as a potential drug target

A gene associated with inflammation could serve as a future drug target for endometriosis.

Following genetic analyses of thousands of women, researchers identified a variant of a gene called NPSR1 linked with more severe cases of endometriosis. It is hoped that this could be the first non-hormonal drug target for the condition, which affects millions of women worldwide.

'This is an exciting new development in our quest for new treatments of endometriosis,' said joint senior author Professor Krina Zondervan, from the University of Oxford. 'We have a promising new nonhormonal target for further investigation and development that appears to address directly the inflammatory and pain components of the disease.'

Endometriosis is a chronic condition where endometrial-like tissue inappropriately grows outside of the uterus, often causing intense pain and, in some cases, infertility. It affects up to 190 million women globally, but treatments are limited to hormonal therapy or surgery that is often ineffective.

The study, published in Science Translational Medicine, was a collaboration between Professor Zondervan's team in Oxford, the University of Wisconsin-Madison, Baylor College of Medicine in Texas and Bayer Pharmaceuticals.

The Oxford team first looked for genetic similarities between 32 families where at least three members had been diagnosed with endometriosis. These results highlighted a common variation in chromosome 7, which the Baylor team confirmed in rhesus macaques (which can also develop endometriosis). The Oxford team then more finely sequenced the DNA region, and found that a significant number of both women and macaques with endometriosis harboured a variation in the same gene – NPSR1. They confirmed the significance of the variant in a further cohort of 11,000 women.

Although this is the first time a gene has been implicated in endometriosis, NPSR1 itself is already linked to other inflammatory diseases such as asthma and arthritis. By blocking the increased inflammatory functions of the NPSR1 variant with an experimental inhibitor from Bayer, the researchers demonstrated reduced pain in mouse models of endometriosis.

Although NPSR1 may be a promising target for some women, not everyone with endometriosis will possess the newly identified variant.

'It's a really magnificent piece of sleuthing,' Professor Linda Griffith, an endometriosis researcher from the Massachusetts Institute of Technology who was not involved with the study told Science. 'It pulls together so many pieces of the puzzle, but it's not the final piece.'