New Target and Drug Candidates for Alleviating Chronic Pain

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Chronic pain is one of the most significant unmet medical needs and health burdens in society today. This is due to limited analgesic efficacy of existing drugs, coupled with adverse side effects, and the development of tolerance over time. Moreover, patients may develop dependence on commonly prescribed opiate-based analgesics, with negative consequences and greatly increased societal costs. Hence there is a pressing need for new targets for drug development and new drug candidates to target chronic pain. During the course of our recently completed ERC grant we screened a number of mouse mutants for sensory neuron phenotypes that might arise from perturbation of neuron growth control mechanisms. We discovered an unexpected phenotype of reduced pain sensitivity in an importin knockout mouse line. Most strikingly, acute knockdown of this specific importin gene had an ameliorating effect in the chronic stage of a neuropathic pain model. Screening for drugs that might mimic this effect lead to the identification of a number of approved drugs that are candidates for repositioning as analgesics. In this PoC we will carry out the following objectives: (1) file for IP protection on the new pain drug target and the initially identified candidate analgesics; (2) validate the new drug target and drug candidates in models of neuropathic and/or chemotherapy-induced chronic pain; (3) devise an HTS-compatible assay for future screening of additional drug leads for chronic pain; and (4) carry out additional IP protection and pre-clinical validation steps to maximize the commercialization potential of this discovery.