DR?1-MOG as a Next-Generation Immunotherapy for Methamphetamine Use Disorder

Methamphetamine use disorder is associated with damage to regions of the brain that control cognitive and psychiatric functionOne third to one half of adults with methamphetamine use disorder experience cognitive impairments and other psychiatric symptoms that significantly impact treatment outcomesincreased relapse and lower treatment retention ratesMounting evidence demonstrates how immune factors can influence addictive behaviors and contribute to relapseWe have shown that recombinant T cell receptor ligandRTLa partial major histocompatibility complexpMHCclass II construct with a tethered myelin peptidepDRMOGaddresses the neuroimmune effects of methamphetamine addiction and offers a new strategy for the treatment of methamphetamine induced central nervous systemCNSinjuryRTLs bind to and downregulate expression of the invariant chain CDthe primary receptor for macrophage migration inhibitory factorMIFa key inflammatory mediator in a number of diseasesincluding methamphetamine and alcohol use disordersPreliminary data in rodent models demonstrate RTL s therapeutic impact on cognitive functiondrug seekingand inflammationA drawback of RTLis that it can only be given to individuals that are DRpositiveTo overcome this limitation we have created DRMOG which has the major advantage that it would be suitable to all people struggling with methamphetamine use disorderThe proposed application builds on our previous research by using complimentary rodent models that will allow us to rapidly move DRMOG along the drug development pipeline toward readiness for clinical translationThe primary objective of this Phase I STTR project is to evaluate the efficacy of DRMOG as a medication for methamphetamine use disorder and test whether DRMOG can promote abstinent like behavior by reducing drug seekingimproving cognitive functionand reducing anxious like behaviorTo accomplish this objectivewe will evaluate the behavioral effects of DRMOG on methamphetamine exposure in two rodent models that will assess self administration behavior and the consequences of neurotoxicbinge like drug exposureSecondary objectives will investigate the effects of DRMOG immunotherapy on methamphetamine induced CNS inflammation by characterizing the effects of DRMOG immunotherapy on the CDNFB inflammatory signaling cascadeCollectivelythese objectives will establish the degree to which specific inflammatory signals contribute to methamphetamine relapse behaviors and methamphetamine induced cognitive and affective dysfunctionWe expect that following the completion of this one year projectwe will have substantial evidence to support a new treatment strategy for methamphetamine use disordera strategy which addresses problems that are central to the underlying pathophysiology of methamphetamine addiction PROJECT NARRATIVE Discovery of a medication that could improve brain repair and recovery following methamphetamine addiction would represent a major scientific breakthrough that could broadly impact addiction treatmentThis project will evaluate a novel medication for methamphetamine use disorder and test whether or not it can promote abstinentlike behavior by reducing relapse and improving cognitive and affective functionA major outcome of the proposed project will be moving closer to readiness for human clinical trials as a new medication to reduce relapse