Traumatic brain injuries (TBI) are an area of significant unmet need with no approved therapeutics and a national burden of ~$77 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 24 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 30 minutes, 3 hours and even at 24 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 ~6 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 Statement: Public Health Relevance: Traumatic brain injuries (TBI) including concussions affect 1.7 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.
NIH Spending Category: Brain Disorders; Emergency Care; Injury (total) Accidents/Adverse Effects; Injury - Childhood Injuries; Injury - Trauma - (Head and Spine); Injury - Traumatic brain injury; Injury - Unintentional Childhood Injury; Neurosciences; Pediatric
Project Terms: Accident and Emergency department; Achievement; Acute; Adverse effects; Affect; Agonist; American; animal efficacy; Animal Model; Animals; Antioxidants; Area; Astrocytes; Attention; Biological Markers; Biomedical Engineering; Brain; Brain Concussion; Brain Edema; Brain Injuries; brain tissue; Businesses; Capital; Caring; Cause of Death; Cell Death; Cell Survival; cell type; cellular targeting; Child; Clinical; Cognitive; cost; Data; Development; disability; Dose; drug candidate; drug development; Drug Kinetics; drug metabolism; Edema; emergency service/first responder; Emotional; Evaluation; Excision; excitotoxicity; experience; Experimental Designs; extracellular; Family suidae; Frequencies (time pattern); Glial Fibrillary Acidic Protein; Gliosis; Glutamates; Goals; Grant; Growth Factor; Healed; healing; Homeostasis; Hospitals; Hour; Human; Hyperactive behavior; improved; In Vitro; in vivo; Industry; Injury; intravenous injection; Investments; Ions; Lead; Leadership; Link; Medical; mild traumatic brain injury; Mitochondria; Modeling; Molecular; Motor; mouse model; Mus; Neonatal; Neuroglia; Neurologic; neuronal survival; Neurons; neuroprotection; novel strategies; operation; Oxidative Stress; Patients; Pharmaceutical Preparations; Pharmacologic Substance; Phase; Phase III Clinical Trials; prevent; Principal Investigator; Process; Production; professor; public health relevance; Purinoceptor; Receptor Signaling; Regimen; relating to nervous system; Research; research and development; restoration; Safety; Signal Transduction; Small Business Innovation Research Grant; Small Business Technology Transfer Research; small molecule; social anxiety; Sports; success; Supporting Cell; Testing; Texas; Therapeutic; Therapeutic Human Experimentation; Time; Toddler; Toxic effect; Traumatic Brain Injury; Treatment Protocols; Universities; Work; young adult
