Scientists discover possible genetic target for treating endometriosis


Date:
November 12, 2020
Source:
Michigan State University
Summary:
Researchers have identified a potential genetic target for treating
an especially painful and invasive form of endometriosis.



FULL STORY ========================================================================== Michigan State University researchers have identified a potential
genetic target for treating an especially 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 in the MSU College of Human
Medicine. Wilson and Jake Reske, a graduate student in the MSU Genetics
and Genome Sciences Program, are first authors of the study.

Their research 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 the
function of cells, run wild, Reske said. This allows the cells that
normally line the uterus to form deep implants outside the uterus and
cause severe pelvic pain.

"There haven't been many successful nonhormonal therapies for this form
of endometriosis that have made it to the bedside yet," Reske said.

In laboratory experiments, he and Wilson tested a drug that appeared to
target the 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 the kind associated with the ARID1A mutation,
can be debilitating for many women, often leading to infertility.

"It can seriously impact women's quality of life and their ability to
have a family and work," said Ronald Chandler, an assistant professor
of obstetrics, gynecology and reproductive biology, who supervised 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 drug they studied targeted a protein in cells called
P300, suppressing the super-enhancers and offsetting the effects of the
ARID1A mutation, Wilson said.

The same type of treatment could be used to treat other forms on
endometriosis, he said.

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

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


========================================================================== Story Source: Materials provided by Michigan_State_University. Note:
Content may be edited for style and length.


========================================================================== Journal Reference:
1. Mike R. Wilson, Jake J. Reske, Jeanne Holladay, Subechhya Neupane,
Julie
Ngo, Nina Cuthrell, Marc Wegener, Mary Rhodes, Marie Adams,
Rachael Sheridan, Galen Hostetter, Fahad T. Alotaibi, Paul J. Yong,
Michael S.

Anglesio, Bruce A. Lessey, Richard E. Leach, Jose M. Teixeira,
Stacey A.

Missmer, Asgerally T. Fazleabas, Ronald L. Chandler. ARID1A
Mutations Promote P300-Dependent Endometrial Invasion through
Super-Enhancer Hyperacetylation. Cell Reports, 2020; 33 (6):
108366 DOI: 10.1016/ j.celrep.2020.108366 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2020/11/201112100858.htm

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