Researchers discover a potential genetic target for the treatment of endometriosis

Reviewed by Emily Henderson, B.Sc.November 11, 2020

Michigan State University researchers have identified a potential genetic target for the treatment of a particularly painful and invasive form of endometriosis.

Their study published in Cell reports, a scientific journal, could lead to better treatments for women suffering from severe forms of endometriosis, said Mike Wilson, a postdoctoral fellow at MSU College of Human Medicine. Wilson and Jake Reske, a graduate student in the MSU Genetics and Genome Sciences program, are the first authors of the study.

Their research has focused on a type of endometriosis that occurs in women who have a mutation in a gene called ARID1A, which is linked to the more invasive and painful form of the disease. When ARID1A is mutated, so-called “super-enhancers,” a part of the DNA that determines cell function, are unleashed, Reske said. This allows the cells that normally line the uterus to form deep implants outside the uterus and cause severe pelvic pain.

There have not been many successful non-hormonal therapies for this form of endometriosis that have made it to the patient’s bed. “

Jake Reske, a graduate student in the MSU Genetics and Genome Sciences program

In lab experiments, he and Wilson tested a drug that appeared to target super enhancers and stop the spread of endometriosis. Such a drug – part of a new type of treatment called “epigenetic therapy” that controls how genes are expressed – could be far more effective than current treatments, including surgery, hormone therapy and pain management.

Endometriosis, particularly that associated with the ARID1A mutation, can be debilitating for many women, often leading to infertility.

“It can have a serious impact on women’s quality of life and their ability to have a family and a job,” said Ronald Chandler, assistant professor of obstetrics, gynecology and reproductive biology, who oversaw the study. “It’s not easy to treat and it can become resistant to hormone therapy. The most clinically effective thing we’ve found is that targeting super enhancers could be a new treatment for this deeply invasive form of the disease.”

The drug they studied targeted a protein in cells called P300, suppressing super-enhancers and offsetting the effects of the ARID1A mutation, Wilson said. The same type of treatment could be used to treat other forms of endometriosis, he said.

Researchers are already planning follow-up studies to find other drugs that could target P300, Wilson and Reske said.

The MSU team collaborated with researchers from the Van Andel Institute, providing them with tissue samples that VAI scientists could analyze with a machine called a next-generation sequencer.