Page last updated September 2021

Researchers identify genetic cause of endometriosis, paving way for new treatment

Female reproductive health concept. Woman hand holding uterus sh

New research has identified the gene NPSR1 as a genetic cause of endometriosis, revealing potential new avenues for treating the disease.

Conducted by the University of Oxford, Baylor College of Medicine, the University of Wisconsin-Madison, and Bayer AG, the research used genetic analysis of humans and rhesus macaques to identify rare NPSR1 variants as the genetic cause of endometriosis.

NPSR1 is a protein coding gene, which means that it works to determine the function of a cell. It also plays a role in inflammation that occurs with other health conditions such as asthma.

The Oxford research team, led by Dr Krina T Zondervan, had previously found a genetic linkage to endometriosis on chromosome seven (7p13-15), by analysing DNA from 32 families where at least three cisgender women had endometriosis and from 105 cisgender women who didn’t have the condition. The team also analysed a genetic dataset of over 3,000 endometriosis cases and 2,300 control cases (people without endometriosis).

Further in-depth sequencing analysis allowed researchers to narrow down to rare variants of NPSR1 as the genetic cause of endometriosis.

Another Oxford study identified a specific common variant in the NPSR1 gene that was associated with stage III/IV endometriosis

Most of the women within the study who carried rare NPSR1 variants had stage III/IV endometriosis, meaning that the variants occurred more often in those with the condition than those without.

Researchers at the University of Wisconsin-Madison and Baylor College of Medicine then corroborated these findings by checking DNA variations in monkeys. They found that the macaque equivalent of the genetic variation of human chromosome seven occurred more frequently in monkeys with endometriosis.

“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,” said Jeffrey Rogers, associate professor at the Human Genome Sequencing Center at Baylor.

“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.”

Another Oxford study of over 11,000 cisgender women, including those both with endometriosis and those without, identified a specific common variant in the NPSR1 gene that was associated with stage III/IV endometriosis.

A drug safe for human use that inhibits NPSR1 activity could, in theory, reduce inflammation and therefore reduce endometriosis pain

The research also identifies NPSR1 as a potential new drug target for endometriosis treatment. Researchers at Bayer, in collaboration with Oxford University, used an NPSR1 inhibitor to block the gene’s protein signalling using cells in the lab and in mouse models of endometriosis. They found that the treatment led to reduced inflammation and abdominal pain — although the drug used is not approved for use on humans.

Still, this opens a new avenue of possibility for drug development. A drug safe for human use that inhibits NPSR1 activity could, in theory, reduce inflammation and therefore reduce endometriosis pain.

“This is an exciting new development in our quest for new treatments of endometriosis, a debilitating and underrecognised disease affecting 190 million women worldwide,” said Dr Zonderman, who is the professor of reproductive and genomic epidemiology, 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.

She continued: “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 nonhormonal target for further investigation and development that appears to address directly the inflammatory and pain components of the disease.”

Endometriosis is a chronic and painful condition in which tissue that mimics the lining of the womb (endometrium) grows elsewhere in the body. This tissue responds to the menstrual cycle in the same way that the endometrium does, which can cause severe pain and other symptoms such as irregular periods.

Endometriosis is estimated to affect up to 10% of people with a vagina.
 
The full findings have been published in Science Translational Medicine
 
 
Featured image is a photo of two cupped hands, holding a coloured-paper cutout of a uterus
 
 
Page last updated September 2021

New research has identified the gene NPSR1 as a genetic cause of endometriosis, revealing potential new avenues for treating the disease.

Conducted by the University of Oxford, Baylor College of Medicine, the University of Wisconsin-Madison, and Bayer AG, the research used genetic analysis of humans and rhesus macaques to identify rare NPSR1 variants as the genetic cause of endometriosis.

NPSR1 is a protein coding gene, which means that it works to determine the function of a cell. It also plays a role in inflammation that occurs with other health conditions such as asthma.

The Oxford research team, led by Dr Krina T Zondervan, had previously found a genetic linkage to endometriosis on chromosome seven (7p13-15), by analysing DNA from 32 families where at least three cisgender women had endometriosis and from 105 cisgender women who didn’t have the condition. The team also analysed a genetic dataset of over 3,000 endometriosis cases and 2,300 control cases (people without endometriosis).

Further in-depth sequencing analysis allowed researchers to narrow down to rare variants of NPSR1 as the genetic cause of endometriosis.

Another Oxford study identified a specific common variant in the NPSR1 gene that was associated with stage III/IV endometriosis

Most of the women within the study who carried rare NPSR1 variants had stage III/IV endometriosis, meaning that the variants occurred more often in those with the condition than those without.

Researchers at the University of Wisconsin-Madison and Baylor College of Medicine then corroborated these findings by checking DNA variations in monkeys. They found that the macaque equivalent of the genetic variation of human chromosome seven occurred more frequently in monkeys with endometriosis.

“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,” said Jeffrey Rogers, associate professor at the Human Genome Sequencing Center at Baylor.

“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.”

Another Oxford study of over 11,000 cisgender women, including those both with endometriosis and those without, identified a specific common variant in the NPSR1 gene that was associated with stage III/IV endometriosis.

A drug safe for human use that inhibits NPSR1 activity could, in theory, reduce inflammation and therefore reduce endometriosis pain

The research also identifies NPSR1 as a potential new drug target for endometriosis treatment. Researchers at Bayer, in collaboration with Oxford University, used an NPSR1 inhibitor to block the gene’s protein signalling using cells in the lab and in mouse models of endometriosis. They found that the treatment led to reduced inflammation and abdominal pain — although the drug used is not approved for use on humans.

Still, this opens a new avenue of possibility for drug development. A drug safe for human use that inhibits NPSR1 activity could, in theory, reduce inflammation and therefore reduce endometriosis pain.

“This is an exciting new development in our quest for new treatments of endometriosis, a debilitating and underrecognised disease affecting 190 million women worldwide,” said Dr Zonderman, who is the professor of reproductive and genomic epidemiology, 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.

She continued: “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 nonhormonal target for further investigation and development that appears to address directly the inflammatory and pain components of the disease.”

Endometriosis is a chronic and painful condition in which tissue that mimics the lining of the womb (endometrium) grows elsewhere in the body. This tissue responds to the menstrual cycle in the same way that the endometrium does, which can cause severe pain and other symptoms such as irregular periods.

Endometriosis is estimated to affect up to 10% of people with a vagina.
 
The full findings have been published in Science Translational Medicine
 
 
Featured image is a photo of two cupped hands, holding a coloured-paper cutout of a uterus
 
 
Page last updated September 2021

Monica Karpinski

Founder & Editor, The Femedic

Monica is the Founder and Editor of The Femedic. She is an award-winning content strategist and healthcare journalist, who created The Femedic to meet a simple need: accurate, genuinely useful health content that answered people’s questions properly. Monica has been named one of The Drum’s 50 under 30 for influential women in digital 2018 and was shortlisted for Female Entrepreneur of the Year in the 2018 British Business awards. She speaks and writes widely on healthcare and health inequalities.

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