SBIR-STTR Award

Astrocyte Activation by Small-Molecule ADORA3 Agonists: a Novel Therapy for Alzheimer's Disease
Award last edited on: 1/11/2022

Sponsored Program
STTR
Awarding Agency
NIH : NIA
Total Award Amount
$297,948
Award Phase
2
Solicitation Topic Code
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Principal Investigator
James D Lechleiter

Company Information

Astrocyte Pharmaceuticals Inc

245 First Street Suite 1800
Cambridge, MA 02142
   (617) 444-8765
   info@astrocytepharma.com
   www.astrocytepharma.com

Research Institution

University of Texas - San Antonio

Phase I

Contract Number: 1R41AG062163-01
Start Date: 9/30/2018    Completed: 11/30/2019
Phase I year
2018
Phase I Amount
$199,830
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.

Project Terms:
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; 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

Phase II

Contract Number: 5R41AG062163-02
Start Date: 00/00/00    Completed: 00/00/00
Phase II year
2019
Phase II Amount
$98,118
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