An end to the crippling pain of endometriosis is now on the horizon with the discovery of a responsible gene and potential target for drugs. Endometriosis involves uterine tissue growing where it shouldn't, usually elsewhere in the abdomen, and is frequently associated with inflammation, bleeding, and pain during periods that can lead to scarring.
In 2007 a team led by Dr Krina Zondervan of Oxford University reported an apparent connection to chromosome 7p13-15, based on families with more than three members affected.
Dr Jeffrey Rogers and colleagues at Baylor College of Medicine confirmed the result in a new study. In Science Translational Medicine the two teams report their findings and follow-up work revealing variants of the NPSR1 gene as the culprits. The rs142885915 variant, which occurs in 11 percent of people with European ancestry, appears to be particularly commonly responsible. The finding is backed up with the discovery the same gene has similar effects in rhesus macaques.
"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," Rogers said in a statement. “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."
Currently, the only proven options for endometriosis are surgery and estrogen-suppressing drugs. Not only do both risk considerable side-effects, but they're not always effective, particularly when the endometrial tissue occurs in places where surgery is imposable.
The authors hope to change this, having demonstrated the NPSR1 inhibitor SHA 68R reduces inflammation in mice with endometriosis. The mice treated with SHA 68R also showed reduced signs of abdominal pain than untreated mice, although this is perhaps harder to measure.
"This is an exciting new development in our quest for new treatments of endometriosis,” Zondervan said. “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.”
NPSR1 variants have previously been found to be associated with asthma, allergies, inflammatory bowel disease, and even panic disorders, although without implicating rs142885915.
Few conditions are as under-researched as endometriosis. It takes women a staggering seven years, on average, to get diagnosed even in wealthy countries. An estimated 50 percent heritability should have hastened the identification of genetic causes, but the well-established pattern of doctors dismissing women who report extreme pre-menstrual pain obstructs research as well as access to treatment. By obscuring the numbers of women who suffer from it (5-10 percent according to most estimates) failures to diagnose have also made the task of finding cures seem less urgent. One study has estimated the true cost of the condition to be similar to type 2 diabetes, but it has gained a fraction of the funding.
Famously, funding was found, however, for a study on whether men found women with rectovaginal endometriosis more attractive and another on how male partners of sufferers are affected.
