New Drug Compounds Show Promise Against Endometriosis

Date

01/31/15

Two new drug compounds – one of which has already proven useful in a mouse model of multiple sclerosis – appear to be effective in treating endometriosis, a disorder that, like MS, is driven by estrogen and inflammation, scientists report in Science Translational Medicine.

The researchers hope to eventually use the new compounds and others like them to treat a variety of disorders linked to estrogen signaling and inflammation: endometriosis, multiple sclerosis, inflammatory breast cancer, liver fibrosis, and cardiovascular and metabolic problems associated with obesity, for example.

The team tested the new compounds in a mouse model of endometriosis (en-doh-mee-tree-OH-sis) and in human endometriotic cells. Both compounds interact with estrogen receptors, signaling proteins that regulate the activity of many genes. Some of these genes contribute to the body’s immune response and promote inflammation.

Endometriosis afflicts as many as 15 percent of reproductive-age women in the U.S. and millions of women around the world. The disorder can lead to scarring of the ovaries, fallopian tubes and other tissues; infertility; inflammation and chronic pain.

“The usual treatments for endometriosis are aimed at suppressing estrogen production because it’s an estrogen-driven disease,” said University of Illinois molecular and integrative physiology professor Benita Katzenellenbogen, who led the new study with chemistry professor John Katzenellenbogen. “We thought that a better approach might be to interfere with both of the main aspects of endometriosis: the growth-promoting actions and also the inflammatory aspects – both of which involve the estrogen receptor,” she said.

Current pharmaceutical treatments can suppress endometriosis, but often fail to reduce the pain and inflammation that are hallmarks of the disorder, said John Katzenellenbogen, whose laboratory 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 said. “There also is unfortunately a high rate of recurrence of the disease.”

The new compounds, OBHS (oxabicycloheptene sulfonate) and CLI (chloroindazole), interact with two types of estrogen receptors (ER-alpha and ER-beta, respectively). Each drug reduced the size of endometriotic tissue or prevented its growth outside the uterus in mice. Each also reduced inflammation and suppressed the development of new neurons and blood vessels that support the misplaced tissue. The treatments did not reduce fertility or the health of young pups born to mouse mothers that had undergone the therapies.

The compounds had similar positive effects in human endometriotic cells that were grown in culture with human immune cells, called macrophages, which can contribute to the inflammation and growth of endometriotic tissue.

The research team also found that adding either of the new compounds to a common endometriosis treatment, letrazole, did a better job of suppressing endometriosis than letrazole alone.

“Inflammation is a driver of endometriosis,“ Benita Katzenellenbogen said. “At some point you’ve got to turn it off, and these compounds turn it off by working through the estrogen receptors.”
In a previous study published in the Proceedings of the National Academy of Sciences, researchers found that CLI suppressed – and even reversed – the loss of brain neuron structure and function in a mouse model of MS.

While many more years of work must be done to test these new compounds in other models and, eventually, in human patients, the work demonstrates a new approach to treating endometriosis and other disorders tied to estrogen signaling and inflammation, the researchers said.

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 supported this research.

The paper, “Dual Suppression of Estrogenic and Inflammatory Activities for Targeting of Endometriosis,” is available online or from the U. of I. News Bureau.

UIUC's News Bureau original article, author - Diana Yates

Custom Tags

Related People

Directory

scheelinAlexander
Scheeline
bjmccallBenjamin
McCall
cmartn10Calgary
Martin
r-gennisRobert
Gennis
j-gerltJohn
Gerlt
sgranickSteve
Granick
mgruebelMartin
Gruebele
hergenroPaul
Hergenrother
huangRaven
Huang
mlkraftMary
Kraft
leckbandDeborah
Leckband
yi-luYi
Lu
martinisSusan
Martinis
snairSatish
Nair
eoldfielEric
Oldfield
rienstraChad
Rienstra
cmsCharles
Schroeder
zanZaida
Luthey-Schulten
sksScott
Silverman
s-sligarStephen
Sligar
zhao5Huimin
Zhao
mselfba2Michelle
Self-Ballard
pbraunPaul
Braun
mdburkeMartin
Burke
jeffchanJefferson
Chan
sdenmarkScott
Denmark
dlottDana
Dlott
foutAlison
Fout
agewirthAndrew
Gewirth
ggirolamGregory
Girolami
shs3Sharon
Hammes-Schiffer
sohirataSo
Hirata
kamihullKami
Hull
jainPrashant
Jain
jkatzeneJohn
Katzenellenbogen
nmakriNancy
Makri
douglasmDouglas
Mitchell
jsmooreJeffrey
Moore
murphycjCatherine
Murphy
r-nuzzoRalph
Nuzzo
dimerPhilip
Phillips
rauchfuzThomas
Rauchfuss
joaquinrJoaquín
Rodríguez-López
jrogersJohn
Rogers
sarlahDavid
Sarlah
kschweizKenneth
Schweizer
jsweedleJonathan
Sweedler
vddonkWilfred
van der Donk
renskeRenske
van der Veen
vuraweisJosh
Vura-Weis
mcwhite7M.
White
sczimmerSteven
Zimmerman
beakPeter
Beak
wklemperWalter
Klemperer
jdmcdonaJ.
McDonald
mvp11Michael
Pak
pogoreloTaras
Pogorelov
mshen233Mei
Shen
dewoonDavid
Woon
wboulangWilliam
Boulanger
rxbRohit
Bhargava
qchen20Qian
Chen
jianjuncJianjun
Cheng
hy66Hong
Yang
andinomaJosé
Andino Martinez
decosteDonald
DeCoste
thhuangTina
Huang
tjhummelThomas
Hummel
dkellDavid
Kell
doctorkMichael
Koerner
marvilleKelly
Marville
crrayChristian
Ray
tlbrownTheodore
Brown
rmcoatesRobert
Coates
thdjrThom
Dunning,
dykstraClifford
Dykstra
j-jonasJiri
Jonas
j-lisyJames
Lisy
shapleyJohn
Shapley
pshapleyPatricia
Shapley
awieckowAndrzej
Wieckowski
zumdahl2Steven
Zumdahl
ksuslickKenneth
Suslick
jlbearJodi
Bear
jcoxJenny
Cox
ealthausEllen
Althaus
staciryStaci
Ryan
sqdSean
Drummond
dmillsDouglas
Mills
sheeleySarah
Sheeley
jsmaddenJoseph
Madden
cknight4Connie
Knight
schulzeHeather
Schulze
slangleySamantha
Langley
ssmurrayStar
Murray
kbaumgarKeena
Finney
adkssnBeatrice
Adkisson
bmylerBeth
Myler
trabari1Katie
Trabaris
kewatsonKaren
Watson
strussTheresa
Struss
metclfKara
Metcalf
ljohnso2Lori
Johnson
jlwJamison
Lowe
jenruslJennifer
Russell
lchenoweLeslie
Chenoweth
jcfJonathan
Freiman
wdedoWolali
Dedo
ebielserElaina
Kutz
spinnerDavid
Spinner
plblumPatricia
Simpson
stevens2Chad
Stevens
lsagekarLori
Sage-Karlson
bertholdDeborah
Berthold
kecarlsoKathryn
Carlson
tlchen4Timothy
Chen
sdesmondSerenity
Desmond
angelaecAngela
Crawford
hsahmed3Hajira
Ahmed
kakinsKenye
Akins
asali3Arzeena
Ali
axelson2Jordan
Axelson
bai11Yugang
Bai
scbakerStephanie
Baker
duffin2Kevin
Duffin
duttadDebapriya
Dutta
pflotschPriscila
Falagan Lotsch
iflemingIan
Fleming
dgrayDanielle
Gray
thennes2Thomas
Hennessey
mhettingMary Jo
Hettinger
holdaNancy
Holda
holler2Jordan
Holler
aibarrAlejandro
Ibarra
kimshSung Hoon
Kim
kocherg2Nikolai
Kocherginsky
philipk2Philip
Kocheril
dlee106David
Lee
legare2Stephanie
Legare
alewandoAgnieszka
Lewandowska
qianliliQianli
Li
bdmccallBirgit
McCall
smccombiStuart
McCombie
jdm5Justin
McGlauchlen
egmooreEdwin
Moore
myerscouKathleen
Myerscough
snalla2Siva
Nalla
oraham2Aaron
Oraham
lah5LeeAnn
Pannebaker
poonawa2Maria
Poonawalla
rrollerR.
Roller
romanovaElena
Romanova
roubakhiStanislav
Rubakhin
vsfVictoria
Shepherd-Fortner
shvedalxAlexander
Shved
asoudaAlexander
Soudakov
ktsween2Kalee
Sweeney
sktarterSamantha
Tarter
aathoma2Andy
Thomas
kwilhelKaren
Wilhelmsen
wilkeyRandy
Wilkey
luxu3Lu
Xu
yuanyao4Yuan
Yao
silongSilong
Zhang
schlembaMary
Schlembach
emccarr2Elise
McCarren
cmercierChristen
Mercier
atimpermAaron
Timperman
niesShuming
Nie
hshanHee-Sun
Han
mmgMutha
Gunasekera