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- 24 September 2021
Page last updated September 2021
Researchers identify genetic cause of endometriosis, paving way for new treatment
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 monkeys to identify rare NPSR1 variants as being linked to 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, found a genetic link 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 then validated these findings by analysing a genetic dataset of over 3,000 endometriosis cases and 2,300 control cases (people without endometriosis).
This allowed researchers to narrow down to rare variants of NPSR1 as being genetically linked to the disease.
Another Oxford study identified a specific common variant in the NPSR1 gene that was associated with stage III/IV endometriosis
They found that most of the women who carried these variants had stage III/IV endometriosis.
Researchers at the University of Wisconsin-Madison and Baylor College of Medicine 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 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 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 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 head of the department 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 monkeys to identify rare NPSR1 variants as being linked to 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, found a genetic link 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 then validated these findings by analysing a genetic dataset of over 3,000 endometriosis cases and 2,300 control cases (people without endometriosis).
This allowed researchers to narrow down to rare variants of NPSR1 as being genetically linked to the disease.
Another Oxford study identified a specific common variant in the NPSR1 gene that was associated with stage III/IV endometriosis
They found that most of the women who carried these variants had stage III/IV endometriosis.
Researchers at the University of Wisconsin-Madison and Baylor College of Medicine 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 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 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 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 head of the department 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
