[Exploring non-hormonal therapies and drug repositioning for endometriosis: insights from mouse model studies]

Osuka S, Satoko Osuka
Nihon yakurigaku zasshi. Folia pharmacologica Japonica · 2024 · vol. 159(6) , pp. 374–380 · doi:10.1254/fpj.24041 · PMID:39496411
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⚙ AI-generated summary by claude@2026-07, 2026-07-27 ⓘ

This study investigated NLRP3 inhibitors and antibiotics for endometriosis in mouse models, finding that NLRP3 inhibition reduced ovarian cysts and antibiotic treatment decreased peritoneal lesions, suggesting non-hormonal therapeutic potential.

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⚙ AI-generated deep summary by claude@2026-06, 2026-06-13 · read from full text ⓘ

This paper reviews two mouse-model studies aimed at identifying non-hormonal, drug-repositioning strategies for endometriosis. In one study, the authors found NLRP3 expression is higher in ovarian endometriosis cysts than in endometrium, and NLRP3 inhibition reduced lesion size in model mice without suppressing endometrial proliferation, which they position as potentially compatible with fertility. In the second study, using a peritoneal lesion model, the authors linked Fusobacterium infection of the endometrium to phenotypic changes in endometrial fibroblasts and showed that bacterial infection increased lesion size, while antibiotic “decontamination” shrank lesions; they also discuss possible reuse of existing drugs with NLRP-inhibitory activity and antibiotic repositioning, while noting the work is preclinical and framed as research insights rather than clinical outcomes. This paper is centrally about endometriosis — it uses mouse model data to explore NLRP3 inhibition and Fusobacterium-targeted approaches as non-hormonal drug repositioning options.

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Abstract

The mainstay of treatment for endometriosis is hormonal therapy, which suppresses ovulation; therefore, patients cannot conceive during treatment. There is a dilemma with ovarian-sparing surgery, known as laparoscopic cystectomy, as it can potentially damage the ovaries. Therefore, there is a need for non-hormonal drug therapies. We addressed these challenges in endometriosis treatment, aiming to maintain ovarian function while achieving effective treatment through basic research. Herein, we present two studies using different mouse models of endometriosis. The first study investigates the effects of a nucleotide-binding oligomerization domain, leucine-rich repeat, and pyrin domain-containing (NLRP) 3 inhibitor in a mouse model of ovarian endometriotic cysts. We confirmed the increased expression of NLRP in ovarian endometriotic cysts compared with that in the uterine endometrium in both patient-derived samples and mouse model lesions. Administering an NLRP3 inhibitor to model mice resulted in lesion reduction. The second study used a peritoneal lesion mouse model to examine bacterial infection in the endometrium and its association with endometriosis development. Using existing databases and patient-derived samples, we identified that Fusobacterium was involved in the development of endometriosis and lesion enlargement when infecting the endometrium in the model. Furthermore, antibiotic treatment led to a reduction in the lesions. These studies highlight the potential of repositioning existing drugs with NLRP3 inhibitory effects or antibiotics as new non-hormonal treatments for endometriosis.
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特集 子宮内膜症の病態解明と画期的な新薬開発に向けた新たな視点 ドラッグリポジショニングをめざした子宮内膜症非ホルモン性治療の検討 2024 年 159 巻 6 号 p. 374-380 詳細 抄録 子宮内膜症の治療の主軸はホルモン療法であるが，排卵を抑制するため，治療中妊娠はできない．子宮内膜症は不妊の要因にもなるため，不妊治療中は内膜症も悪化しより状況が悪くなるという悪循環に陥る．一方で，卵巣温存手術である卵巣子宮内膜症性嚢胞摘出術は，卵巣にダメージを与えるというジレンマがある．以上より，非ホルモン性の薬物治療が望まれている．当教室では，これら子宮内膜症治療の問題点の解決をめざし，卵巣機能の維持と両立する治療につながる臨床研究や基礎研究に取り組んできた．このうち子宮内膜症モデルマウスを用いた2つの研究を紹介する．一つ目は，卵巣子宮内膜症性嚢胞のモデルマウスを用いて，nucleotide-binding oligomerization domain, leucine-rich repeat, and pyrin domain-containing（NLRP）3阻害薬の作用を検討したものである．患者由来検体ならびに，マウスモデルの病変において，卵巣子宮内膜症性嚢胞では，子宮内膜に比して，NLRP3の発現が亢進していることを確認した．子宮内膜での発現は，子宮内膜症併存の有無によって変化を認めなかった．モデルマウスへの阻害薬の投与により，病変が縮小することを確認した．NLRP3の阻害は，着床の場である子宮内膜の増殖を抑制しないことから，挙児希望と両立する治療法になる可能性が示唆された．既存薬でもNLRP3阻害作用を持つ薬剤があり，内膜症治療への応用も期待される．二つ目は，腹膜病変マウスモデルを用いた子宮内膜への細菌感染と子宮内膜症発生についての検討である．既存データベースならびに，患者由来検体から，子宮内膜症の発生に子宮内膜へのフソバクテリウム感染による子宮内膜線維芽細胞の表現型変化が関与することをつきとめた．モデルマウスでの検討では子宮内膜へのフソバクテリウム感染により病変が増大すること，さらに，抗菌薬投与による除菌の結果，病変が縮小することを確認した．NLRP阻害作用を持つ既存薬剤，抗菌薬のドラッグリポジショニングが，子宮内膜症の新しい非ホルモン性治療となる可能性が示された． © 2024 公益社団法人 日本薬理学会

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endometriosis

MeSH descriptors

Disease Models, Animal Disease Models, Animal Disease Models, Animal Disease Models, Animal Disease Models, Animal Disease Models, Animal Disease Models, Animal Disease Models, Animal Disease Models, Animal Disease Models, Animal Disease Models, Animal Disease Models, Animal Disease Models, Animal Disease Models, Animal Disease Models, Animal Disease Models, Animal Disease Models, Animal Disease Models, Animal Disease Models, Animal Disease Models, Animal

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