Antifibrotic Medicines May Be Effective Therapies in Endometriosis, Preclinical Study Suggests

Antifibrotic Medicines May Be Effective Therapies in Endometriosis, Preclinical Study Suggests

Two compounds — antifibrotic medicines that inhibit tissue scarring — successfully stopped processes involved in the development and progression of endometriosis, a study in cells and a mouse model of the condition showed.

The results support the targeting of the Wnt/β-catenin pathway as a new therapeutic approach for endometriosis, the researchers said.

The study, “β-Catenin Signaling Inhibitors ICG-001 and C-82 Improve Fibrosis in Preclinical Models of Endometriosis”, was published in the journal Scientific Reports.

Although several therapeutic alternatives, including hormonal therapy and surgery, are available to treat endometriosis patients, recurrence rates are high. Thus, more effective treatments are needed, the researchers said.

Fibrosis, the overgrowth and scarring of different tissues, is an integral part of endometriotic lesions, along with resistance to cell death and increased cell proliferation. In fact, some researchers believe it is time to redefine endometriosis — currently described as the “presence of endometrial epithelial and stromal cells at ectopic sites” — to highlight its pro-fibrotic nature.

Investigators at Oita University in Japan tested two experimental antifibrotic medicines to find out whether they were effective against endometriotic lesions in cell dishes and in mice.

The two compounds, ICG-001 and C-82, interfere with a cellular signaling pathway known as Wnt/β-catenin, which plays a critical role in the development and maintenance of adult tissues.

This signaling pathway has been implicated in wound repair and fibrosis. It also has been associated with fibrotic lung, skin, kidney, and liver diseases.

Importantly, “studies on fibrosis in endometriosis have reported a possible correlation between aberrant activation of the Wnt/β-catenin signaling pathway and progression of endometriosis,” the researchers said.

To test the effectiveness of ICG-001 and C-82, researchers extracted endometriotic cyst stromal cells (ECSCs) from ovarian endometriosis tissues of patients and normal endometrial stromal cells (NESC) from normal endometrium tissues of healthy people (controls).

Analysis of the different cells revealed that β-catenin expression in ECSC was significantly higher than in NESC.

Both ICG-001 and C-82 significantly inhibited cell viability and proliferation and migration of ECSCs, as well as increased apoptosis — a form of programmed cell death — in these cells.

The researchers then tested the in vivo (in the body) effects of ICG-001 in a mouse model of endometriosis. The team found that ICG-001 was not toxic to the abdominal organs of the animals. It also was found to significantly reduce the number and weight of endometriotic lesions, and decrease fibrosis.

There were some limitations to their study, the team acknowledged. Specifically, the mouse model used in the study may not accurately reflect human endometriosis. In addition, the high dose of ICG-001 given to the mice may not be comparable to a clinical dose.

However, the investigators said that ICG-001 and C-82 are “leads to promising therapeutic agents for the treatment of endometriosis.”

“Our data suggest that CBP/β-catenin inhibitors [Wnt/β-catenin pathway inhibitors] have a possibility not only to prevent but reduce fibrosis in endometriosis,” they concluded.

“Future studies will need to focus on searching and synthesizing more effective CBP/β-catenin inhibitors. The promotion of research and practical application of new drugs for endometriosis is important, and a clinical trial of CBP/β-catenin inhibitors for endometriosis should be planned for the near future,” they added.