Targeting lipid rafts for treatment of migraine

PROJECT SUMMARY Migraine is a highly prevalent condition with an extraordinarily negative impact on quality of life and represents a heavy socioeconomic burden to the societyprimarily because of decreased working efficiency and workdays lostManagement of migraine has become increasingly pharmacological during recent yearsWhile several therapeutic options existmost of the prophylactic drugs currently available have partial ameliorating effect on headache with frequent treatment limiting side effectsMany patients do not respond or achieve complete relief of migraine associated pain highlighting a continuing need for new therapeutic modalitiesIn this proposala collaboration initiated between Raft Pharmaceuticals LLC and the University of California in San DiegoUCSDseeks to fully evaluate RFTan agent that interferes with lipid rafts and has been found to reverse light aversiveness induced by the CompoundRFTwill be further evaluated for efficacy and safety to determine its suitability for further developmentEfficacy studies to be performed at UCSD will determine the full range of efficacy of RFTincluding appropriate route of administration and dose response relationships that will determinebest route andminimum effective doseA second model of chemicallynitroglycerininduced migraine will test RFTto confirm efficacy in an orthogonal preclinical modelIn both pre clinical modelsthe UCSD team will examine functional effects on pain centers using immunohistochemistryRaft Pharmaceuticals will determine exposure margins for the described efficacy studies and further delineate mechanistic components of RFTeffects by examination of activity versus a subset of nociceptors relevant to migraineThese studies will establish mechanistic insight in support of observed in vivo resultsFinallyRaft will examine whether RFTdemonstrates a reasonable safety margin in a repeat dose safety studyCollective data from this proposal will determine utility and feasibility of RFTfor development as a migraine therapeutic Narrative The objective is to discover and develop new drugs for treating pain caused by migrainea leading cause of discomfort and disability in patients in the US and worldwide and there is a significant need for novel therapies