Genetic Mutation Found In Endometriosis Patients Could Lead to New Treatment

New research has identified a potential genetic mutation found in people with severe forms of endometriosis in the hopes of stopping the spread of the disease. 

Researchers out of Michigan State University (MSU) are testing a drug that targets mutations of the ARID1A gene — a gene that is linked to severe endometriosis. When this gene mutates, “super-enhancers” (a part of the DNA that determines the function of the cell) “run wild,” causing the cells that normally line the uterus to form outside the uterus, i.e. endometriosis. By targeting this specific gene mutation, scientists are hoping they can treat or prevent the disease from spreading in the body.

“ARID1A — the gene that we're studying — is frequently mutated in deeply invasive forms of endometriosis,” Ronald Chandler, PhD, assistant professor of obstetrics, gynecology and reproductive biology at Michigan State University College of Human Medicine, tells Verywell. “Certain forms of endometriosis can be severely debilitating and really impact quality of life.”

There’s no cure for endometriosis, so Chandler says severe cases of endometriosis are often treated with hormone therapy or surgery. Using a drug that targets genetic mutations associated with the disease—treatment called epigenetic therapy—is an emerging area of research, and may be more effective than current treatments. Chandler and his team’s findings were published this month in the journal Cell Reports.

“Sometimes, patients become resistant to hormone therapy, and there's really no other options at that point other than surgery and pain management,” Chandler says. “It [epigenetic therapy] might be something implemented in the future as a potential non-hormonal therapeutic option.” 

Cause of Endometriosis 

Endometriosis occurs when tissue that normally lines the uterus grows outside of the uterus in places that it should not be, like the pelvic cavity, ovaries and fallopian tubes. It can be incredibly painful, and causes symptoms like pelvic pain, severe menstrual cramps, pain during sex, heavy or irregular menstrual bleeding, and even infertility. 

Many people go years misdiagnosed or undiagnosed with endometriosis, Chandler says, as the only way to definitely diagnose it is through laparoscopic investigation, which is a minimally invasive surgery. 

According to the Endometriosis Foundation of America, the disease affects one in 10 reproductive-aged individuals or an estimated 200 million worldwide. Experts aren’t sure the exact cause of endometriosis, but researchers like Chandler have found some people with the condition have specific genetic mutations.

Paul Yong, MD, PhD, an associate professor of gynecological specialties at the University of British Columbia, has also researched the role of genetic mutations in endometriosis. In 2017, Yong and fellow researchers published a study that found a set of genetic mutations in samples from 24 women with benign endometriosis. They found the most common mutations, seen in five women, occurred in genes including ARID1A, PIK3CA, KRAS and PPP2R1A.

Aside from being associated with endometriosis, mutations in these genes are associated with a serious type of ovarian cancer, clear cell carcinoma.

Like Chandler’s research, Yong’s study is important because it further looks at the genetic component of the disease and the role of mutations within endometriosis cells (somatic mutations). Whereas the inherited genetic component that makes someone predisposed to developing the disease has been greatly studied before, Yong’s research examined the genetic changes that are not inherited, and are instead developed during one's life.

By identifying mutations in endometriosis cells, the hope is to improve the way the disease is treated—the same objective Chandler described.

“With the research that we are doing right now, we're trying to determine the functional role of these somatic mutations: are they associated with the cells being more invasive, are they associated with certain types of pain or potentially infertility?” Yong says.

“If that's the case, then I would suggest that treatments targeted to the gene mutations might be a novel way of treating the disease.”

How Endometriosis Is Treated

There are three primary ways endometriosis is treated currently, including pain management, hormonal treatments, and surgery. While hormonal treatment can be effective, it’s not a viable option for people who are trying to get pregnant, Yong says. 

Because endometriosis is a recurring disease, Chandler says surgery may not solve the problem long-term. Some patients will have no endometriosis for years after surgery, while others will see its return almost immediately.

Laparoscopic surgery can remove endometriosis lesions, but depending on where they are located, it can be incredibly painful for the patient, he says. “It's treatable, but not curable, and sometimes it can actually get worse over time.”

Because endometriosis can be so painful for patients and lead to serious outcomes like infertility, Chandler says it’s important researchers not only find better ways to treat it but to detect it, too. Living with the condition can greatly affect people’s quality of life so it’s important the medical community takes it seriously. 

“It's very common for women not to be definitively diagnosed for years—it can be decades—and I think a lot of it has to do with doctors… attributing [the pain] to having painful periods,” Chandler says. “There's really a need to look more closely to identify biomarkers and other ways to really diagnose women and find alternatives to hormone therapy (because that can affect fertility), and recognize how the disease impacts quality of life.”