Boston Children's Hospital has received a USD 3.9 million NIH R01 grant to identify specialized pro-resolving lipid mediator (SPM) receptors as druggable targets for endometriosis-associated pain — a condition that current therapies fail to adequately control in many patients and that contributes to opioid dependence and overdose risk.
The award, funded primarily by the National Institute of Neurological Disorders and Stroke (NINDS) and administered by the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), supports preclinical work by principal investigator Michael Sean Rogers. The research builds on the team's prior finding that docosahexaenoic acid (DHA), eicosapentaenoic acid (EPA), and several SPMs derived from those omega-3 fatty acids rapidly eliminate pain and reduce lesion size in a validated mouse model of endometriosis.
SPMs are endogenous lipids that resolve inflammation. The research program aims to identify which SPMs are most active in vivo, map those molecules to their cognate G-protein coupled receptors (GPCRs) using the PRESTO-Tango near-complete human non-olfactory GPCR library, and determine which cell types express those receptors through single-cell RNA sequencing of both human endometriotic lesions and the mouse model. Identifying a tractable GPCR target would enable conventional high-throughput screening for small-molecule agonists that replicate SPM activity without the pharmacokinetic liabilities.