eLife Assessment: Kynurenine monooxygenase blockade reduces endometriosis-like lesions, improves visceral hyperalgia, and rescues mice from a negative behavioural phenotype in experimental endometriosis

Omowumi T. Kayode
2024 · doi:10.7554/elife.99226.1.sa2 · W4401255893
peer-review OA: gold CC0
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⚙ AI-generated summary by claude@2026-06, 2026-06-08 ⓘ

Kynurenine monooxygenase inhibition with KNS898 in a mouse endometriosis model reduced lesion size, improved pain behaviors, and rescued negative behavioral phenotypes.

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⚙ AI-generated deep summary by claude@2026-06, 2026-06-08 ⓘ

This paper investigated whether kynurenine monooxygenase (KMO) is expressed in endometriosis lesions and whether pharmacologic inhibition using the oral KMO inhibitor KNS898 reduces lesion and pain-like phenotypes in a mouse model. Using immunohistochemistry on human eutopic endometrium and endometriosis tissues, the authors found KMO strongly expressed in epithelial components of lesions, and in mice they showed that oral KNS898 produced measurable KMO blockade with increased kynurenine/kynurenic acid and reduced 3-hydroxykynurenine. In experimental endometriosis, KNS898 treatment lowered endometriosis-like distended endometrial gland-like structure (DEGLS) burden and improved endometriosis pain-like behaviors even when treatment started one week after lesion initiation, with a reported caveat that lesion size/volume did not differ despite changes in burden and that body weight effects occurred after inoculation. This paper is centrally about endometriosis — targeting KMO with KNS898 to reduce endometriosis-like lesions and pain-related behaviors.

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Abstract

Endometriosis is a common and debilitating neuro-inflammatory disorder that is associated with chronic pain. Definitive diagnosis is based on the presence of endometrial-like tissue (lesions) in sites outside the uterus. Kynurenine monooxygenase (KMO) is a mitochondrial enzyme of tryptophan metabolism that regulates inflammation and immunity. Here, we show that KMO is expressed in epithelial cells in human endometriosis tissue lesions and in corresponding lesions in a mouse model of endometriosis. In mice, oral treatment with the potent KMO inhibitor KNS898 induced a biochemical state of KMO blockade with accumulation of kynurenine, diversion to kynurenic acid and ablation of 3-hydroxykynurenine production. In the mouse model of endometriosis, KMO inhibition improved histological outcomes and endometriosis pain-like behaviours, even when KNS898 treatment commenced one week after initiation of lesions. Taken together, these results suggest that KMO blockade is a promising new non-hormonal therapeutic modality for endometriosis.

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Condition tags

endometriosis

Citation neighborhood

Papers in the corpus that this work cites (lower rings, blue) and that cite this one (upper rings, green). Dot size scales with the paper's in-corpus citation count — bigger dot = more influential within the endo/adeno field. Click a dot to open that paper. [ expand to 2 hops ] — adds papers reached through this work's immediate citers/citees. Heavier; up to 60 extra dots.

References (20)

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last seen: 2026-06-10T17:14:06.276822+00:00
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