Stabilization of the Alveolar-Capillary Barrier with ARF6 Inhibitor as a Treatment for Severe Influenza

SUMMARYInfluenzavirusinfectionisoneofthemostcommonacuterespiratorydiseasesandremainsoneofthelargestdiseaseburdensonhumanswithsevereprimaryviralpneumoniaoftenresultingindeathThepathogenicityofinfluenzaincludesahostresponsethatcanincludeaseveresystemicinflammatoryreactioncytokinestormandensuingvascularleakVascularleakisafundamentalelementinthepathogenesisofcirculatoryshockandmultipleorganfailurewhichcanleadtodeathininfluenzapatientsThelaboratoriesofDrDean Licofounder and former Chief Scientific Officer of Navigenand DrShannon Odelbergalong withNavigenhavedemonstratedthatvascularleakassociatedwithinflammationismediatedbyactivationofthesmall GTPaseARFa common nodal point in the signaling pathways of several inflammatory cytokines andgrowth factorsNavigen s objective is to reduce morbidity and mortality associated with influenza infections bymodifyingthishostresponseSpecificallyweproposetoevaluatetheefficacyofoursmallmoleculeARFinhibitorswiththehypothesisthatinhibitionofARFwillreducevascularleakelicitedbytheinfectionwhilehaving no adverse effect on immunitybased clearance of the virusNARRATIVEInfluenzainfectionremainsoneofthelargestdiseaseburdensonhumanswithsevereprimaryviralpneumoniaoftenresultingindeathThepathogenicityincludesahostresponsethatcanincludeaseveresystemicinflammatoryreactionandensuingvascularleakNavigenhasdemonstratedthatvascularleakassociated with inflammation is mediated by activation of the small GTPase ARFand proposes to evaluate itssmallmolecule ARFinhibitors in a mouse model of H Ninfection