Ending the hurt

Alex Eben Meyer

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For the one in ten women who suffer from endometriosis, pain is a part of daily life: back pain, menstrual cramps, pain during sex, intestinal pain.

“They often suffer in silence,” says Yingqun Huang, a professor of obstetrics, gynecology, and reproductive sciences at the Yale School of Medicine.

“Endometriosis is a taboo.” Researchers, too, have been relatively silent on the topic of endometriosis. Decades of pushing endometriosis into the underfunded margins of medical research has led to imprecise treatments and a poor understanding of the disease’s causes.

However, new research by Huang may shed light on the cause of the disease. In a recently published study in the Journal of Clinical Investigation, her team identified a potential cellular culprit that can trigger endometriosis. What’s more, they believe that targeting this cell type with drugs could treat the disease.

Endometriosis is characterized by the growth of uterus-like tissue outside of the uterus. The researchers sifted through the different cell types in these outgrowths until they noticed something intriguing: a prominent group of immune cells called macrophages that expressed high levels of a  molecule called TET3. Huang’s group had previously seen TET3 in uterine fibroids and other organs, and its presence was sometimes a harbinger of disease. “We know high TET3 is bad in the liver, in the muscle, and in type 2 diabetes,” Huang says. She had a suspicion that high TET3 might be bad news in the uterus too.

To test whether TET3-overexpressing macrophages cause endometriosis, Huang’s team reduced TET3 on macrophages in mice with endometriosis. This killed the TET3-overexpressing macrophages, decreased the disease’s severity, and reduced inflammation. Huang realized this could be key to treating endometriosis. “Until now, there is no marker to target endometriosis,” she says. “By using a molecule that will target TET3, we have the potential to kill the bad macrophages.”

Her team identified a molecule that can target TET3—and treating mice with that molecule eliminated the culprit cells. Huang is now working to turn this into a drug that is safe and effective for humans with endometriosis. She even thinks that targeting TET3 could help treat other diseases that involve inflammation. “Killing these macrophages is like stepping on the brakes,” she says.