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Hope for endometriosis drug target

Tuesday August 31st 2021

A potential drug treatment for endometriosis could available after a gene that increases the risk of the condition was identified.

Researchers from the University of Oxford, Baylor College of Medicine, the University of Wisconsin-Madison and Bayer AG found NPSR1 during genetic analyses of humans and rhesus macaques.

Dr Krina Zondervan, of Oxford University, led the team that previously found a genetic linkage to endometriosis on chromosome 7p13-15 after analysing DNA from families with at least three women diagnosed with endometriosis.

The Baylor team, led by Dr Jeffrey Rogers, verified the genetic linkage in the DNA of rhesus monkeys with spontaneous endometriosis at the Wisconsin National Primate Research Center at the University of Wisconsin-Madison.

When further in-depth sequencing analysis of the endometriosis families at Oxford it narrowed down the genetic cause to rare variants in the NPSR1 gene.

Most of the women carrying these rare variants had stage III/IV disease. When the Baylor researchers sequenced rhesus monkeys they also showed suggestive evidence.

An Oxford study of more than 11,000 women, including patients with endometriosis and healthy women, went on to identify a specific common variant in the NPSR1 gene also associated with stage III/IV endometriosis.

The findings are published in Science Translational Medicine.

Dr Rogers, of the Human Genome Sequencing Center at Baylor, said: “This is one of the first examples of DNA sequencing in nonhuman primates to validate results in human studies and the first to make a significant impact on understanding the genetics of common, complex metabolic diseases.

“The primate research really helped to provide confidence at each step of the genetic analysis in humans and gave us motivation to carry on chasing these particular genes.”

The Bayer and Oxford researchers used an NPSR1 inhibitor to block protein signalling of that gene in cellular assays and then in mouse models of endometriosis and found it led to reduced inflammation and abdominal pain.

Dr Krina Zondervan, head of the Department of Women’s and Reproductive Health at the University of Oxford and co-director of the Endometriosis CaRe Centre at Oxford, said: “This is an exciting new development in our quest for new treatments of endometriosis, a debilitating and under recognised disease affecting 190 million women worldwide.

“We need to do further research on the mechanism of action and the role of the genetic variants in modulation of the gene’s effects in specific tissues. However, we have a promising new non-hormonal target for further investigation and development that appears to address directly the inflammatory and pain components of the disease.”

Neuropeptide S receptor 1 is a nonhormonal treatment target in endometriosis Science Translational Medicine 25 August 2021

[abstract]

Tags: Genetics | North America | UK News | Women's Health & Gynaecology

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