ASTROCYTE ACTIVATION BY SMALL MOLECULE P2Y1 AGONISTS FOR TREATMENT OF TBI

DESCRIPTION provided by applicant Traumatic brain injuries TBI are an area of significant unmet need with no approved therapeutics and a national burden of $ billion annually Astrocyte Pharmaceuticals is developing a small molecule pharmaceutical agent that would be administered by intravenous injection by emergency responders or a medical professional within hours of injury to limit neuronal damage and cell death The proprietary approach at Astrocyte Pharmaceuticals differs significantly from historical neuroprotective attempts in that it focuses on a non neuronal cell type the astrocyte which has only recently received broader attention as an important cellular target for successful therapeutic research Molecular activation of astrocytes enhances multiple healing mechanisms including protection against edema glutamate excitotoxicity and oxidative stress Preliminary data demonstrate significant neuroprotective benefits of these molecules in mouse models when administered within minutes hours and even at hours post injury The goal of this STTR Phase I project is to establish the ability of these small molecules to significantly enhance the inherent neuroprotective activity of astrocytes in both small and large animal TBI models The project aims to optimize the treatment protocol dosing timing and frequency that maximizes the in vitro neuronal viability benefits of candidate molecules utilize an in vivo mouse TBI model to select a lead candidate that maximizes reduction in the magnitude and duration of whole brain edema and reactive gliosis biomarkers and validate that the efficacy of the lead candidate in a study with a toddler piglet TBI model PUBLIC HEALTH RELEVANCE Traumatic brain injuries TBI including concussions affect million Americans annually and are the leading cause of death and disability in children and young adults Through this grant Astrocyte Pharmaceuticals aims to develop the first therapeutic for TBI patients which would limit neural damage and the associated physical cognitive and or emotional impacts of this distressingly common injury