Alzheimer's disease (AD) is an area of significant unmet need that creates a national burden of ~$259 billion annually. AD is the leading cause of dementia, affecting 10% of Americans over the age of 65. Demographic shifts and the age-related nature of AD will soon place this disease as the costliest health care expenditure in the U.S. with a projected impact of $1.1 trillion per year by 2050. Current therapies target secondary aspects of the disease to temporarily and modestly ease symptoms; there no FDA-approved therapies that slow progression or cure the disease. According to the Alzheimer's Association, a breakthrough drug would treat the underlying disease and stop or delay the cell damage that eventually leads to the worsening of symptoms. The first disease-modifying neuroprotective therapeutic will clearly represent a global medical innovation. Astrocyte Pharmaceuticals Inc. is developing a small molecule, AST-004, for acute brain injury patients. The proprietary approach at Astrocyte Pharmaceuticals differs significantly from historical neuron-centric neuroprotective attempts by focusing on a non-neuronal cell type, the astrocyte. Astrocytes have only recently received broader attention as an important cellular target for successful therapeutic research. The protective pathways activated by AST-004 are conserved in ex vivo human brain tissue. AST-004 has demonstrated significant neuroprotective efficacy in various acute animal models of ischemic stroke and traumatic brain injury. AST-004 has a favorable pharmaceutical profile that is amenable to chronic treatment of CNS diseases such as AD. Preliminary data show that AST-004 treatment also increases astrocyte and neuronal viability in a mouse model of AD. This Phase I STTR proposal will (1) define the neuroprotective efficacy of AST-004 in two mouse models of AD and (2) validate the neuroprotective efficacy of AST-004 in highly relevant fresh cortical brain samples from human AD patients. The overall goal of this AST-004 development project is to slow the onset and severity of AD-caused neurodegeneration.
Public Health Relevance Statement: PROJECT NARRATIVE Approximately 5 million Americans over age 60 suffer from Alzheimer's disease (AD); this number is projected to surpass 13 million by 2050. The available FDA-approved pharmacotherapies are able to ease symptoms, but afford only modest and temporary benefit. Astrocyte Pharmaceuticals Inc. aims to develop the first disease- modifying neuroprotective AD therapeutic that can slow or reverse the progression of the disease.
NIH Spending Category: Acquired Cognitive Impairment; Aging; Alzheimer's Disease; Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD); Brain Disorders; Dementia; Injury (total) Accidents/Adverse Effects; Injury - Trauma - (Head and Spine); Injury - Traumatic brain injury; Neurodegenerative; Neurosciences
Project Terms: 3xTg-AD mouse; Achievement; Acute; Acute Brain Injuries; Address; Adenosine A3 Receptor; Affect; Age; age related; Agonist; Alzheimer's Disease; Alzheimer's disease model; American; Animal Model; Antioxidants; Area; Astrocytes; Attention; Biopsy Specimen; Brain; Brain Diseases; Brain Injuries; brain tissue; Caliber; Capital; Cell Death; cell injury; Cell Survival; cell type; cellular targeting; Central Nervous System Diseases; Chronic; chronic traumatic encephalopathy; clinical development; clinical efficacy; Clinical Research; Data; Dementia; Development; Disease; disease phenotype; Disease Progression; Dose; drug development; drug discovery; efficacy testing; Excision; extracellular; FDA approved; frontal lobe; frontotemporal degeneration; Glutamates; Goals; Growth Factor; Head; healing; Health; Health Expenditures; healthspan; Homeostasis; Human; human old age (65+); Human Pathology; improved; in vivo; Individual; innovation; Investigation; Investigational New Drug Application; Investments; Ions; Ischemic Stroke; J20 mouse; Lesion; Medical; Mitochondria; Modeling; mouse model; Mus; Nature; Nerve Degeneration; Neurodegenerative Disorders; Neuroglia; Neurologic Deficit; Neurons; neuroprotection; Neuroprotective Agents; Normal Pressure Hydrocephalus; novel; novel strategies; novel therapeutics; Oral; Parkinsonian Disorders; Pathway interactions; Patients; Pharmaceutical Preparations; Pharmacologic Substance; Pharmacotherapy; Phase; pre-clinical; Presenile Alzheimer Dementia; Privatization; Process; Production; professor; Progressive Supranuclear Palsy; Property; Punch Biopsy; Rattus; Research; restoration; Risk; Sampling; scale up; Severities; Shunt Device; Slice; Small Business Innovation Research Grant; Small Business Technology Transfer Research; small molecule; stroke model; success; Supporting Cell; Symptoms; targeted treatment; Testing; Texas; Therapeutic; Therapeutic Human Experimentation; Toxicology; Traumatic Brain Injury; Universities
