Astrocyte activation by small-molecule ADORA3 agonists: a novel therapy for Alzheimer's disease

PROJECT SUMMARY Alzheimerandapos s diseaseADis an area of significant unmet need that creates a national burden of$billion annuallyAD is the leading cause of dementiaaffectingof Americans over the age ofDemographic shifts and the age related nature of AD will soon place this disease as the costliest health care expenditure in the U Swith a projected impact of $trillion per year byCurrent therapies target secondary aspects of the disease to temporarily and modestly ease symptomsthere no FDA approved therapies that slow progression or cure the diseaseAccording to the Alzheimerandapos s Associationa breakthrough drug would treat the underlying disease and stop or delay the cell damage that eventually leads to the worsening of symptomsThe first disease modifying neuroprotective therapeutic will clearly represent a global medical innovationAstrocyte Pharmaceuticals Incis developing a small moleculeASTfor acute brain injury patientsThe proprietary approach at Astrocyte Pharmaceuticals differs significantly from historical neuron centric neuroprotective attempts by focusing on a non neuronal cell typethe astrocyteAstrocytes have only recently received broader attention as an important cellular target for successful therapeutic researchThe protective pathways activated by ASTare conserved in ex vivo human brain tissueASThas demonstrated significant neuroprotective efficacy in various acute animal models of ischemic stroke and traumatic brain injuryASThas a favorable pharmaceutical profile that is amenable to chronic treatment of CNS diseases such as ADPreliminary data show that ASTtreatment also increases astrocyte and neuronal viability in a mouse model of ADThis Phase I STTR proposal willdefine the neuroprotective efficacy of ASTin two mouse models of AD andvalidate the neuroprotective efficacy of ASTin highly relevant fresh cortical brain samples from human AD patientsThe overall goal of this ASTdevelopment project is to slow the onset and severity of AD caused neurodegeneration PROJECT NARRATIVE Approximatelymillion Americans over agesuffer from Alzheimerandapos s diseaseADthis number is projected to surpassmillion byThe available FDA approved pharmacotherapies are able to ease symptomsbut afford only modest and temporary benefitAstrocyte Pharmaceuticals Incaims to develop the first diseasemodifying neuroprotective AD therapeutic that can slow or reverse the progression of the disease