Endometriosis is a painful condition in which tissue inside the uterus, known as the endometrium, develops outside the uterus. Up to 10 percent of women experience it worldwide. The condition is chronic, exceedingly painful, and can lead to infertility, and it, like many other conditions solely affecting women, remains enigmatic due to decades of neglect by researchers and doctors.
Scientists know little about this condition: How and why it develops is still unknown, and currently, there is no cure. While treatments like painkillers, surgery, and hormonal contraceptives are available to improve pain and infertility, they aren't always effective.
A new research by the University of Oxford, Baylor College of Medicine, the University of Wisconsin-Madison, and Bayer AG scientists have now brought us one step closer to discovering a potential new target for treatment by doing genetic analyses of humans and rhesus macaques, according to a study published in the Science Translational Medicine.
The discovery goes back to a 2015 study at Oxford University. Researchers looked at 32 families containing three or more endometriosis patients and discovered a genetic link between stage III/IV endometriosis and the 7p13-15 region of the human genome, finding that up to 50 percent of endometriosis risk in women is due to genetics.
But finding the specific genes wasn't easy, which is why it took several more years of research at the Baylor College of Medicine. Researchers discovered a variant in the gene NPSR1, which is found on chromosome 7p13-15, that appears to enhance the likelihood of developing late-stage endometriosis. After sequencing the DNA of 849 macaques, 135 of them had acquired spontaneous 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 from the Baylor College of Medicine.
Then, researchers at Oxford sequenced the DNA of almost 11,000 women, including 3,000 women with endometriosis, to discover if there was a similar genetic variation in people. Their findings revealed that stage III/IV endometriosis is linked to the same particular NPSR1 gene variation reported in macaques.
Not every endometriosis patient studied at Oxford University had an NPSR1 variant, which means that if a drug is targeting this subtype, it is unlikely to be effective for everyone, according to a report published on The Conversation. However, it's still promising. During experiments on mice that had pieces of uterine lining implanted into their abdomens to mimic endometriosis, researchers inhibited the NPSR1 gene's expression, and as a result, the mice showed evidence of reduced inflammation and abdominal pain.
"We need to do further research on the mechanism of action and the role of the genetic variants in the modulation of the gene's effects in specific tissues," said genetic epidemiologist Krina T. Zondervan from Oxford University. "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."
As the next step, the researchers plan to undertake more studies on NPSR1 variations and their functional implications in macaques to determine if the gene can be targeted in monkeys in the same way it can be in mice. They can then begin testing drug treatments in preparation for human clinical trials. This landmark study opens the door to the development of anti-NPSR1 medicines that might relieve endometriosis symptoms without disrupting the menstrual cycle and causing hormonal changes, potentially helping millions of women affected by the condition.