New compounds could lead to new treatment for endometriosis

Date: Jan-22-2015 Endometriosis is a condition that affects some 15% of child-bearing age women in the US and millions of other

women around the world. It occurs when tissue that behaves like the lining of the womb or the endometrium is found

outside the womb. Now researchers show how two new compounds that target key drivers of the condition - estrogen

signaling and inflammation - show promise as a new treatment for endometriosis.

Endometriosis causes painful and heavy periods, inflammation and infertility. It affects 15% of child-bearing women in the US.

The study - led by the University of Illinois at Urbana-Champaign - is published in the journal Science

Translational Medicine.

The researchers hope that one day the new compounds will also treat a variety of other conditions where estrogen

signaling and inflammation play a key role. These conditions include multiple sclerosis, liver fibrosis, inflammatory

breast cancer, and obesity-linked cardiovascular and metabolic problems.

Current drugs for treating endometriosis suppress the condition, but they often fail to reduce the pain and

inflammation that characterize it, says John Katzenellenbogen, research professor of chemistry at Illinois, and whose

lab developed the new compounds.

"Current treatments also have side effects on other tissues through which estrogens work, and so they can't be taken

forever," he adds. "There also is unfortunately a high rate of recurrence of the disease."

Compounds tackle growth promotion and inflammation via estrogen receptors

Endometriosis causes painful or heavy periods. It can also cause chronic pain in the lower abdomen, pelvis or lower

back. Women with the condition can also suffer from fatigue and depression. In the long term, endometriosis can lead to

scarring of the ovaries, fallopian tubes and other tissues, plus inflammation and infertility.

For their study, Prof. Katzenellenbogen and colleagues tested the new compounds - chloroindazole (CLI) and

oxabicycloheptene sulfonate (OBHS) - in mice with endometriosis and in human endometriotic cells.

Both compounds block estrogen receptors - signaling proteins that regulate a range of genes, including some that

affect immune response and promote inflammation.

While the usual treatments for endometriosis target estrogen production, the team thought a better approach might be

to target both main aspects of the condition: growth promotion and inflammation. Both of these features involve the

estrogen receptor.

OBHS and CLI interact with two types of estrogen receptor - ER-alpha and ER-beta, respectively.

When they tested them on mice, the researchers found each drug reduced the amount of endometriotic tissue or

prevented its growth outside the uterus. Each drug also reduced inflammation and stopped the growth of new neurons and

blood vessels that support the misplaced womb tissue.

Further tests showed that the pups of mother mice that had the treatment were healthy and did not have reduced

fertility.

Addition of either compound improved effectiveness of letrazole to treat endometriosis

The team also found that adding either compound to letrazole - a drug commonly used to treat endometriosis - made

the treatment more effective than letrazole alone.

When they tested the drugs in human endometriotic cells cultured with macrophages - a type of immune cell that can

contribute to the inflammation and growth of endometriotic tissue - the researchers found they had similar positive

effects on estrogen-dependent activity and inflammation.

Benita Katzenellenbogen, a professor in the School of Molecular and Cellular Biology at Illinois, says:

"Inflammation is a driver of endometriosis. At some point, you've got to turn it off, and these compounds turn it off

by working through the estrogen receptors."

Although the study shows the new compounds offer a potential new approach to the treatment of endometriosis and

other disorders involving estrogen signaling and inflammation, the researchers see many years of work ahead of them

before they can be used in humans.

Funds for the study came from the Eunice Kennedy Shriver National Institute of Child Health and Human Development

and the National Institute of Diabetes and Digestive and Kidney Diseases at the National Institutes of Health.

In June 2014, Medical News Today learned how the study of endometriosis took a leap forward when

researchers announced they had developed a new mouse model for endometriosis.

Written by Catharine Paddock PhD

Not to be reproduced without permission.

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Courtesy: Medical News Today Note: Any medical information available in this news section is not intended as a substitute for informed medical advice and you should not take any action before consulting with a health care professional.