Tau/TIA1 aggregation inhibitors for the treatment of AD

PROJECT SUMMARY Alzheimerandapos s Disease is a neurodegenerative disease characterized by a progressive decline in cognitive function and a corresponding accumulation ofamyloid plaques and neurofibrillary tanglesthe two hallmark pathologiesDrugs currently available to AD patients manage the disease symptoms by improving neuronal activitybut efficacy diminishes as the disease advancesIn tauopathies such as ADthe accumulation of tau correlates closely with neuronal loss and decline of cognitive functionThe novel targeted approach to AD drug development proposed by Aquinnah Pharmaceuticals stems from discoveries made by DrBen WolozinBoston University and co founder of Aquinnahand his labin which tau pathologyin both AD brain samples and animal modelswas observed to be present in stress granulesSGAquinnah is advancing these compelling findings to identify molecules that inhibit the formation of tau SGs as a novel treatment for AD !The overall objective of this SBIR Phaseapplication is to develop several different biologically relevant tau SG assays to select the most promising and biologically relevant hits from our currently ongoing HTSwhich will then be evaluated further for exploratory ADME and brain penetration analysisThe successful completion of this PhaseSBIR will result in the identification of compounds that modulate tau SGs and are candidates for a Phasemedicinal chemistry hit to lead and lead optimization program to further develop as novel drugs for the treatment of AD Project Narrative Alzheimerandapos s Disease is a significant burden to society for which there are currently no effective treatmentswhich means there is a dire need for novel therapeutic approaches in this fieldThis proposal aims to optimize new therapeutic compounds that prevent and reverse stress granule aggregatesand to develop a lead drug candidate that can be tested in animal models and brought to the clinic!