NEURANO BIOSCIENCE LLC — Department of Health and Human Services SBIR Phase I: NIDA

Description

ABSTRACTOpioid use in the United States has been at epidemic proportions for over five yearsConcerted efforts across the spectrum of politicalsocial awarenessclinical and research initiatives have so far been unable to curb the rising rates of opioid use across the countryFrom the treatment standpointa number of novel therapies to alleviate the severe opioid withdrawal symptoms and or reduce risk of relapse continue to be proposedMemantinean FDA approved NMDA receptor antagonisthas shown encouraging results as an adjunct to existing opioid use therapiesIts therapeutic efficacy likely derives from its preferential binding to NMDA receptors located outside the synapsesince broad spectrum NMDA receptor antagonists are associated with multiple clinical side effectsFurthermorepre clinical literature suggests that extrasynaptic NMDARs are preferentially targeted by cocaine and alcoholalthough opioid effects on this receptor population remain unknownWe designed a nanostructured version of memantineAuMthat physically prevents its binding to synaptic NMDA receptorsbut allows activation of extrasynaptic receptors with potency exceeding that of free memantineIn studies performed in different labsAuM has been demonstrated to exclusive target extrasynaptic NMDA receptors while exhibiting pronounced neuropeptide effects in several neurological disease modelsIn this proposal we will use a pre clinical model to evaluate AuM targeting of extrasynaptic NMDA receptors as treatment of opioid withdrawal symptomsa hallmark of opioid use disorder and a major reason for high rates of relapse among chronic opioid users PUBLIC HEALTH RELEVANCE STATEMENTRising rates of the opioid use despite a concerted effort to address the opioid epidemic in the United States urge the development and testing of novel therapeutic approachesMemantinean FDA approved antagonist of NMDA receptorswas shown to suppress symptoms of opioid withdrawal and relapse when used at low concentrations and together with existing opioid use treatmentsThe full extent of potential therapeutic effects of memantine remains undeterminedbecause higher concentrations of memantine trigger serious side effects due to undesirable inhibition of synaptic NMDA receptorsWe propose that restricting the interaction of memantine to a limited population of NMDA receptors in the brain using a nanobiological approach will dramatically enhance its therapeutic efficacy and help to treat opioid use disorders more efficiently