
Inhibition of the enzyme kynurenine monooxygenase (KMO) reduces the development of endometriosis lesions and improves pain-related behaviors in a mouse model of the disease.


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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.

### Competing Interest Statement

The following authors have interests to declare: S.P.W., D.J.M. are co-founders of Kynos Therapeutics Ltd. D.J.M. is a Board Member of Kynos. The University of Edinburgh controls Patents WO2015/091647, WO2016/097144, WO2016/188827 that relate to inhibitors of KMO inhibitors, and include the compound used in this paper. The remaining authors declare no competing interests

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

kynurenine-monooxygenase-inhibition-reduces-endometriosis-lesions-and-improves-pain-behaviors-in-a-mouse-model


Kynurenine Monooxygenase Inhibition Reduces Endometriosis Lesions and Improves Pain Behaviors in a Mouse Model
