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Principal Investigator: Erez Eitan
Organization: NEURODEX INC
Fiscal Year: 2024
Award: $942,163
Funding agency: National Institute of Neurological Disorders and Stroke
PROJECT SUMMARY
In this Fast Track SBIR application, NeuroDex, Inc. proposes to use its expertise in extracellular vesicle (EV)
immunoaffinity isolation to develop a blood test that detects synucleinopathies with high sensitivity, with the long-
term goal of helping clinicians identify patients for whom antipsychotic drugs are harmful and contraindicated.
Development and commercialization of a sensitive blood test for synucleinopathies would address a
major unmet need for selecting appropriate antipsychotic treatments that avoid severe adverse effect.
The proposed work leverages a proprietary procedure NeuroDex developed for isolating EVs from plasma using
immunoaffinity for cell-specific surface markers. Using this approach, the company demonstrated a > 20-fold
increase in signal to noise ratio of NDEs, a degree of specificity that is essential for analyzing aSYN because >
90% of aSYN in plasma does not originate in the brain and is not disease related. Previous efforts to measure
aSYN in unprocessed plasma have not yielded any diagnostic value, but measurement after NDE isolation
provides powerful classification. Leveraging this approach, NeuroDex has developed assays to test aSYN within
and on the surface of neuron-, microglia-, and oligodendrocyte-derived EVs. These assays successfully
distinguished 35 healthy controls, 51 PD patients, and 30 MSA patients with high accuracy. NeuroDex now
proposes to complete the discovery phase (Phase I) and conduct analytical and clinical validation (Phase II).
PHASE I—Aim 1. Identify final biomarkers to be included in the synucleinopathy detection panel. Using
195 samples from healthy individuals and patients with an array of autopsy-confirmed synucleinopathies, we will
assess the performance of different panels of the possible biomarkers to select the combination with the best
performance. Success Metric: ≥ 80% PPV for identifying patients with synucleinopathies and ≥ 90% NPV. Aim
2. Qualify the selected assays. Success Metrics: precision CoV ≤ 20%, linearity across 8-fold dilution range,
and LLQ compatible with clinical samples. Go/No Go Criterion for Progression to Phase II: Completion of the
discovery phase to include a defined set of biomarkers in a panel that a) provides ≥ 90% NPV and b) can be
measured in a robust manner (variability in precision and reproducibility <20%). PHASE II—Aim 1. Analytical
validation of the diagnostic assay. Milestones & Success Metrics: 1) Successful audits for CLIA lab SOP, 2)
analytical data package for FDA breakthrough designation submission. Aim 2. Preliminary clinical validation
of the diagnostic assay in a CLIA-certified lab. We will validate the assays with 700 samples from patients
with dementia with or without synucleinopathies and age-matched controls. Milestones & Success Metrics:
primary: NPV ≥ 90%; secondary: PPV ≥ 80%. Impact—Development and rigorous validation of a novel blood
test for differential diagnosis of dementia with synuclein pathology would produce a commercially-viable
diagnostic to inform appropriate treatment plans and clinical trial stratification for improved drug development.
Terms: <AD dementia><Address><Adverse effects><Age><Alzheimer Type Dementia><Alzheimer beta-Protein><Alzheimer disease dementia><Alzheimer sclerosis><Alzheimer syndrome><Alzheimer's><Alzheimer's Amyloid beta-Protein><Alzheimer's Disease><Alzheimer's amyloid><Alzheimers Dementia><Amentia><American><Amyloid Alzheimer's Dementia Amyloid Protein><Amyloid Beta-Peptide><Amyloid Protein A4><Amyloid beta-Protein><Amyloid β><Amyloid β-Peptide><Amyloid β-Protein><Antipsychotic Agents><Antipsychotic Drugs><Antipsychotics><Arteriosclerotic Dementia><Assay><Autopsy><Aβ><Bioassay><Biological Assay><Biological Markers><Blood><Blood Plasma><Blood Reticuloendothelial System><Blood Sample><Blood Tests><Blood Vessels><Blood specimen><Brain><Brain Nervous System><Brain region><CLIA accredited><CLIA approved><CLIA certified><CLIA compliant><CLIA licensed><Cell Body><Cell Communication and Signaling><Cell Signaling><Cells><Cessation of life><Classification><Clinical><Clinical Trials><Cognitive Disturbance><Cognitive Impairment><Cognitive decline><Cognitive function abnormal><Coronaviridae><Coronavirus><Data><Death><Degenerative Neurologic Disorders><Dementia><Dementia with Lewy Bodies><Detection><Development><Diagnosis><Diagnostic><Differential Diagnosis><Disease><Disorder><Disturbance in cognition><Drowsiness><Drugs><Dysautonomia-Orthostatic Hypotension Syndrome><Dysautonomic Orthostatic Hypotension><Encephalon><Goals><Hematologic Tests><Hematological Tests><Hematology Testing><Hortega cell><Impaired cognition><Individual><Intracellular Communication and Signaling><LB pathology><Lewy Bodies><Lewy body pathology><Lewy pathology><Life><MT-bound tau><Major Tranquilizers><Major Tranquilizing Agents><Measurement><Measures><Medical><Medication><Methods><Microglia><Multiple System Atrophy><Multiple System Atrophy Syndrome><Multisystem Atrophy><Multisystemic Atrophy><NAC precursor><Nerve Cells><Nerve Degeneration><Nerve Unit><Nervous System Degenerative Diseases><Neural Cell><Neural Degenerative Diseases><Neural degenerative Disorders><Neurocyte><Neurodegenerative Diseases><Neurodegenerative Disorders><Neuroleptic Agents><Neuroleptic Drugs><Neuroleptic Malignant Syndrome><Neuroleptics><Neurologic Degenerative Conditions><Neuron Degeneration><Neurons><Noise><Oligodendrocytes><Oligodendrocytus><Oligodendroglia><Oligodendroglia Cell><PARK1 protein><PARK4 protein><Paralysis Agitans><Parkinson><Parkinson Disease><Parkinsonian><Parkinsonian Condition><Parkinsonian Diseases><Parkinsonian Disorders><Parkinsonian Syndrome><Parkinsonism><Pathology><Patient Care><Patient Care Delivery><Patients><Performance><Pharmaceutical Preparations><Phase><Physicians><Plasma><Plasma Serum><Primary Parkinsonism><Primary Senile Degenerative Dementia><Procedures><Prognosis><Progressive Autonomic Failure><Qualifying><Reproducibility><Reticuloendothelial System, Serum, Plasma><SBIR><SNCA><SNCA protein><Sampling><Shy-Drager Syndrome><Shy-Drager Type Idiopathic Orthostatic Hypotension><Signal Transduction><Signal Transduction Systems><Signaling><Small Business Innovation Research><Small Business Innovation Research Grant><Somnolence><Specificity><Stratification><Surface><Symptoms><Systematics><TAR DNA-binding protein 43><TDP-43><TDP43><Testing><Validation><Vascular Dementia><Work><a beta peptide><a-syn><a-synuclein><abeta><ages><alpha synuclein><alpha synuclein gene><alphaSP22><amyloid beta><amyloid-b protein><asyn><beta amyloid fibril><bio-markers><biologic marker><biological signal transduction><biomarker><biomarker discovery><brain cell><care for patients><care of patients><caring for patients><cell type><cognitive dysfunction><cognitive loss><commercialization><common symptom><corona virus><degenerative diseases of motor and sensory neurons><degenerative neurological diseases><design><designing><developmental><diagnostic ability><diagnostic assay><diagnostic capability><diagnostic power><diagnostic utility><diagnostic value><drug development><drug/agent><extracellular vesicles><gitter cell><high risk><improved><mesoglia><microglial cell><microgliocyte><microtubule bound tau><microtubule-bound tau><necropsy><neural degeneration><neurodegeneration><neurodegenerative><neurodegenerative illness><neurological degeneration><neuronal><neuronal degeneration><non A-beta component of AD amyloid><non A4 component of amyloid precursor><novel><patient stratification><perivascular glial cell><postmortem><prevent><preventing><primary degenerative dementia><protein TDP-43><protein TDP43><senile dementia of the Alzheimer type><sleepiness><soluble amyloid precursor protein><stratified patient><success><synuclein><synucleinopathy><tau><tau Proteins><tau factor><treatment planning><validations><vascular><vascular contributions to dementia><α synuclein gene><α-syn><α-synuclein><τ Proteins>