Page URL:

Possible epigenetic target for endometriosis treatment

16 November 2020
Appeared in BioNews 1072

Targeting epigenetic changes caused by gene mutations could potentially treat a severe form of endometriosis, a recent study has reported. 

Normal functioning of the ARID1A gene ensures that DNA sequences, termed super-enhancers, keep genes turned off. Invasive endometriosis is associated with mutations in the ARID1A gene, which results in epigenetic changes and genes being turned on. As a result, cells in the uterus start growing into other tissues and women experience painful periods and potential infertility. 

'There haven't been many successful nonhormonal therapies for this form of endometriosis that have made it to the bedside yet', said Jake Reske from Michigan State University, who is first author of the research, published in the journal Cell Reports.

By comparing normal and ARID1A-deficient cells, the research team showed that ARID1A mutations resulted in a specific epigenetic change. Loss of ARID1A function allows a certain protein, P300, to activate the super-enhancer DNA. This makes drug targeting of P300 a new avenue for epigenetic therapy. 

In laboratory experiments, the small molecule A-485, which binds and inhibits P300, suppressed the super-enhancers and prevented cell invasion. The researchers, however, did not treat mice prone to endometriosis with A-485. 

Endometriosis affects one in ten women and 'can seriously impact women's quality of life and their ability to have a family and work,' said Dr Ronald Chandler, assistant professor of obstetrics, gynaecology and reproductive biology, who led the study. 'It's not easy to treat, and it can become resistant to hormone therapy. The most clinically impactful thing we found is that targeting super-enhancers might be a new treatment for this deeply invasive form of the disease.'

The researchers are already planning their next experiments, which include discovering other drugs which inhibit P300. They believe that targeting P300 could also be more effective than hormone therapy in other forms of endometriosis. 

ARID1A mutations promote P300-dependent endometrial invasion through super-enhancer hyperacetylation
Cell Reports |  10 November 2020
Scientists discover possible genetic target for treating endometriosis
Michigan State University |  10 November 2020
11 October 2021 - by Daniel Jacobson 
Having undiagnosed endometriosis can lead to a lower chance of having a baby following fertility treatment, compared to women who have endometriosis, but have had it diagnosed before starting treatment....
31 August 2021 - by Christina Burke 
A gene associated with inflammation could serve as a future drug target for endometriosis...
22 June 2020 - by Dr Rosie Morley 
Women with endometriosis may have epigenetic differences in uterine cells compared to women without the disease...
14 January 2019 - by Eleanor Mackle 
A protein has been identified as the reason why endometriosis causes infertility, according to a new study...
15 May 2017 - by Isobel Steer 
Cancer-related mutations have been found in tissue taken from patients with deep endometriosis...
to add a Comment.

By posting a comment you agree to abide by the BioNews terms and conditions

Syndicate this story - click here to enquire about using this story.