Investigating ticagrelor in a preclinical pipeline as a novel therapeutic to prevent preterm birth

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dc.contributor.authorArman, B.M.
dc.contributor.authorBinder, N.K.
dc.contributor.authorde Alwis, N.
dc.contributor.authorBeard, S.
dc.contributor.authorGarg, A.
dc.contributor.authorKaitu’u-Lino, T.J.
dc.contributor.authorHannan, N.J.
dc.date.issued2024
dc.description.abstractPreterm birth remains a significant global health challenge, affecting approximately 10% of pregnancies and resulting in one million deaths globally every year. Tocolytic agents, used to manage preterm labour, have considerable limitations including lack of efficacy, and adverse side effects, emphasising the urgent need for innovative solutions. Here, we explore repurposing an antiplatelet cardioprotective drug, ticagrelor, as a potential treatment to prevent preterm birth. Ticagrelor has demonstrated pleiotropic actions beyond platelet inhibition, including relaxant effects on smooth muscle cells and anti-inflammatory effects in models of diabetes and sepsis. As preterm birth is underscored by inflammatory processes triggering uterine contractions, these actions position ticagrelor as an attractive candidate for prevention or delay of preterm birth. Utilising primary human myometrial tissue, human myometrial cells, and a mouse model of preterm birth, we investigated ticagrelor’s potential as a safe and effective therapy for preterm birth. We showed that ticagrelor did not reduce the frequency or strength of spontaneous muscle contractions of ex vivo myometrial tissue nor did it reduce in vitro inflammation-induced contractility in myometrial cells. Additionally, ticagrelor did not exhibit the anticipated anti-inflammatory effects in myometrial cell culture experiments. In our mouse model of preterm birth, ticagrelor neither improved the preterm birth rate or fetal survival outcomes. Gene expression of pro-inflammatory cytokines and contraction-associated proteins in postpartum mouse uteri were unaltered by ticagrelor. In conclusion, ticagrelor is not a strong candidate to continue investigations in clinical trial for the treatment of preterm labour and prevention of preterm birth.
dc.description.statementofresponsibilityBridget M Arman, Natalie K Binder, Natasha de Alwis, Sally Beard, Anjali Garg, Tu'uhevaha J Kaitu'u-Lino, Natalie J Hannan
dc.identifier.citationReproduction, 2024; 167(3):e230404-1-e230404-11
dc.identifier.doi10.1530/REP-23-0404
dc.identifier.issn1470-1626
dc.identifier.issn1741-7899
dc.identifier.orcidArman, B.M. [0000-0003-0314-378X]
dc.identifier.urihttps://hdl.handle.net/2440/144543
dc.language.isoen
dc.publisherBioScientifica
dc.relation.granthttp://purl.org/au-research/grants/nhmrc/1146128
dc.relation.granthttp://purl.org/au-research/grants/nhmrc/1159261
dc.rights© 2024 the author(s). Published by Bioscientifica Ltd. https://rep.bioscientifica.com
dc.source.urihttps://doi.org/10.1530/rep-23-0404
dc.subjectpreterm birth; ticagrelor; tocolytic agents
dc.titleInvestigating ticagrelor in a preclinical pipeline as a novel therapeutic to prevent preterm birth
dc.typeJournal article
pubs.publication-statusPublished

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