Inhibiting soluble epoxide hydrolase as a treatment for chemotherapy inducedperipheral neuropathic pain

Project Summary Investigating the broader efficacy of sEH inhibition and specifically our IND candidateEChas indicated that it is efficacious against chemotherapy induced peripheral neuropathyCIPNThis painful neuropathy develops from chemotherapy treatmentis notoriously difficult to treatand can lead to discontinuation of life prolonging cancer treatmentsThusnew therapeutic approaches are urgently neededWe propose here to test the efficacy of our soluble epoxide hydrolase inhibitorECand a potential backupECfor their efficacy in CIPN and to characterize this activity with three classes of chemotherapeutics in models of CIPNWe will also investigate if EChas potential drug drug interaction with approved chemotherapeutics or alters immune cells functionWe will assess the effects of sEHI on the lipid metabolome and probe for changes in endoplasmic reticulum stress and axonal outgrowth in neuronsThe PK ADME properties of EChave been determined and a pilotday safety study in dogs has been completed with good resultsWe propose here to more fully characterize the analgesic potential of our compound and investigate on and off target actions in CIPN models and model systems relevant to cancer therapy Project Narrative Initial data investigating the broader efficacy of the EicOsis IND candidate ECindicate efficacy against the pain of chemotherapy induced peripheral neuropathyCIPNThe overall goal of EicOsis is to develop a drug candidate for IND enabling studies for the treatment of diabetic neuropathic painHoweverbecause CIPN is a condition with no adequate treatmentwe propose to further explore efficacy and characterize the activity of ECand a backup ECin this chronic pain model