Ph.D. Candidate University of Southern California Irvine, California
Presentation Description: Identification of novel targets/innovative methods for the development of alcohol use disorder (AUD) and alcoholic liver disease (ALD) medications is critical due to the lack of therapies. Our laboratory has established that P2X4 receptors (P2X4Rs) partly regulate ethanol intake and that positive modulation by avermectins (ivermectin [IVM]; moxidectin) reduced ethanol intake in mice. Unfortunately, the lipophilic properties of IVM that promote CNS penetration also promote P-glycoprotein (Pgp) efflux, thereby limiting IVMs utility for CNS disorders. To address this, we found that a combinatorial strategy utilizing a hepatoprotective flavonoid that inhibits Pgp, dihydromyricetin (5 and 10 mg/kg), combined with IVM, lowers the dose of IVM needed to reduce ethanol intake and preference in male C57BL/6J mice by 1.6X. This development of a combinatorial therapy that aims to reduce ethanol intake/preference and provide hepatoprotection against ethanol injury represents a novel strategy for patients suffering from AUD and the subsequent development of ALD.
Upon completion, participants will be able to contemplate novel medications development strategies for alcohol use disorder (AUD) and alcohol-related organ damage (AROD).
Upon completion, participants will be able to develop novel CNS therapeutic options by utilizing unique combinatorial strategies.
Upon completion, participants will be able to consider novel repurposing techniques for targeted therapies.