SBIR-STTR Award

Rapid saliva test for noninvasive diagnostic screening of MCI and dementia In 2020, over 6.2 million Americans had dementia costing the nation $355 billion. There is unmet need for a standardized, cost-effective test for diagnostic screening of Mild cognitive impairment (MCI) and Alzheimer's disease (AD) to move towards early detection and treatment of dementia to reduce disease burden and costs. The goal of this SBIR project is to develop a rapid saliva test for diagnosis of MCI and AD. Phase I showed feasibility of key innovations: standardized saliva methods, validated biomarker assays, 10 candidate biomarkers of MCI and AD and a new saliva cartridge for commercial Lateral Flow Immunoassay (LFA). The proposed Phase II study will clinically validate a diagnostic biomarker of MCI and AD biomarker in older adults and develop a prototype device to show feasibility of the commercial product. SA1 will enroll N=400 males and females age ≥50 at 2 sites: N=200 AD, N=100 MCI and N=100 cognitively normal controls (CN). Participants will be assigned to the cohorts based on a gold standard clinical and neurocognitive evaluation. The cohorts will be matched on important demographics and clinical characteristics. The proposed sample size is estimated to provide ≥80% statistical power with 95% error margin. N=550 saliva samples will be collected: 1 sample from all AD, MCI and 70 CN and 6 serial samples from 30 CN. SA2 will measure the 10 candidate biomarkers in N=550 saliva samples from SA1. Statistical modeling of Training set (N=300) will utilize both statistical and machine learning methods to select a composite biomarker and a cutoff based on diagnostic performance for MCI and AD. Potential demographic and clinical covariates will be included in the statistical model. The selected biomarker and cutoff will be validated using clinically and demographically matched Validation set (N=100) based on targeted milestones for diagnostic accuracy, sensitivity and specificity. Serial samples from CN will define the normal range of biomarker concentration and biological variability. SA3 will demonstrate a prototype LFA device for the MCI-AD biomarker validated in SA2. Expected Outcomes: Results of the Phase II study will rigorously clinically validate a new saliva biomarker for diagnosis of MCI and AD. Large and representative sample size (400 subjects across MCI and AD phenotype and stage, age, sex and geography) will provide statistically significant, generalizable clinical data. Standardized preanalytical saliva handing and analytically validated assays will provide accurate and reliable biomarker data. Prototype device will show technical feasibility of the commercial test. Overall, this project has a high potential for a wide-ranging impact on clinical AD care by providing an objective, noninvasive and clinically feasible biological biomarker for diagnosis of AD and MCI, and translating this innovation into a standardized, scalable and cost-effective point- of-care (POC) test for routine dementia screening in the general population. The proposed product has a strong commercial potential based on a proven and low risk LFA device with known and achievable FDA path, competitive patent portfolio, limited competition and key opinion leaders committed to clinical adoption.

Public Health Relevance Statement:
PROJECT NARRATIVE Rapid saliva test for noninvasive diagnostic screening of MCI and dementia This project will develop a new device, a rapid saliva test for diagnostic screening of Alzheimer's disease and its early stage, the Mild Cognitive Impairment (MCI). The new test will provide increased access, acceptability and deliverability of early dementia diagnosis in community settings aiming to delay disease progression, extend the healthy, active years of life and save costs.

Project Terms:
Accounting; Adoption; Age; ages; Elderly; advanced age; elders; geriatric; late life; later life; older adult; older person; senior citizen; Alzheimer's Disease; AD dementia; Alzheimer; Alzheimer Type Dementia; Alzheimer disease; Alzheimer sclerosis; Alzheimer syndrome; Alzheimer's; Alzheimer's disease dementia; Alzheimers Dementia; Alzheimers disease; Primary Senile Degenerative Dementia; dementia of the Alzheimer type; primary degenerative dementia; senile dementia of the Alzheimer type; Biological Assay; Assay; Bioassay; Biologic Assays; Buffers; Cohort Studies; Concurrent Studies; Diagnosis; Disease; Disorder; Education; Educational aspects; Female; Geography; Goals; Gold; Hand; Health; Health Services Accessibility; Access to Care; access to health services; access to services; access to treatment; accessibility to health services; availability of services; care access; health service access; health services availability; service availability; treatment access; Human; Modern Man; Immunoassay; male; Methods; Statistical Models; Probabilistic Models; Probability Models; statistical linear mixed models; statistical linear models; NIH; National Institutes of Health; United States National Institutes of Health; Neuropsychologies; neuropsychologic; Neuropsychology; Patents; Legal patent; Racial Group; Racial Stocks; Race; Risk; Saliva; Sensitivity and Specificity; Specificity; Standardization; Technology; Testing; Translating; rho; Measures; Health Care Costs; Health Costs; Healthcare Costs; Diagnostic tests; Normal Range; Normal Values; Cost of Illness; Disease Costs; Sickness Cost; base; human subject; Lateral; Site; Chronic; Clinical; Phase; Biological; biologic; Evaluation; Training; Sample Size; Disease Progression; non-invasive diagnosis; non-invasive diagnostic; noninvasive diagnostic; noninvasive diagnosis; Diagnostic; Research Specimen; Specimen; Life; Amentia; Dementia; Neurocognitive; American; early detection; Early Diagnosis; Performance; Accuracy of Diagnosis; diagnostic accuracy; cohort; Participant; General Public; General Population; Devices; Modeling; Sampling; response; disorder control; disease control; Dose; Data; Clinical Data; Cognitive; Enrollment; enroll; Small Business Innovation Research Grant; SBIR; Small Business Innovation Research; Validation; Characteristics; sex; point of care; Pathway interactions; pathway; disease phenotype; salivary assay; saliva assay; saliva based assay; saliva based test; saliva test; salivary test; cost; burden of illness; burden of disease; disease burden; years of life lost to disability; years of life lost to disease; digital; design; designing; Outcome; cost effective; innovation; innovate; innovative; Early treatment; early therapy; Alzheimer disease screening; Alzheimer screening; demographics; prototype; clinical care; community setting; candidate marker; candidate biomarker; Biological Markers; bio-markers; biologic marker; biomarker; phase 2 study; phase II study; screening; mild cognitive impairment; mild cognitive disorder; diagnostic biomarker; diagnostic marker; diagnostic screening; biomarker validation; marker validation; Alzheimer's disease biomarker; Alzheimer's biomarker; Alzheimer's disease biological marker; Alzheimer's biological marker; statistical and machine learning; machine learning method; machine learning based method; machine learning methodologies; Alzheimer's disease diagnosis; Alzheimer's diagnosis; Alzheimer's disease care; Alzheimer's care; cost estimate; cost estimation; saliva sample; salivary sample; lateral flow assay; lateral flow test; point of care testing

Rapid saliva test for noninvasive diagnostic screening of MCI and dementia In 2020, over 6.2 million Americans had dementia costing the nation $355 billion. There is unmet need for a standardized, cost-effective test for diagnostic screening of Mild cognitive impairment (MCI) and Alzheimer's disease (AD) to move towards early detection and treatment of dementia to reduce disease burden and costs. The goal of this SBIR project is to develop a rapid saliva test for diagnosis of MCI and AD. Phase I showed feasibility of key innovations: standardized saliva methods, validated biomarker assays, 10 candidate biomarkers of MCI and AD and a new saliva cartridge for commercial Lateral Flow Immunoassay (LFA). The proposed Phase II study will clinically validate a diagnostic biomarker of MCI and AD biomarker in older adults and develop a prototype device to show feasibility of the commercial product. SA1 will enroll N=400 males and females age ≥50 at 2 sites: N=200 AD, N=100 MCI and N=100 cognitively normal controls (CN). Participants will be assigned to the cohorts based on a gold standard clinical and neurocognitive evaluation. The cohorts will be matched on important demographics and clinical characteristics. The proposed sample size is estimated to provide ≥80% statistical power with 95% error margin. N=550 saliva samples will be collected: 1 sample from all AD, MCI and 70 CN and 6 serial samples from 30 CN. SA2 will measure the 10 candidate biomarkers in N=550 saliva samples from SA1. Statistical modeling of Training set (N=300) will utilize both statistical and machine learning methods to select a composite biomarker and a cutoff based on diagnostic performance for MCI and AD. Potential demographic and clinical covariates will be included in the statistical model. The selected biomarker and cutoff will be validated using clinically and demographically matched Validation set (N=100) based on targeted milestones for diagnostic accuracy, sensitivity and specificity. Serial samples from CN will define the normal range of biomarker concentration and biological variability. SA3 will demonstrate a prototype LFA device for the MCI-AD biomarker validated in SA2. Expected Outcomes: Results of the Phase II study will rigorously clinically validate a new saliva biomarker for diagnosis of MCI and AD. Large and representative sample size (400 subjects across MCI and AD phenotype and stage, age, sex and geography) will provide statistically significant, generalizable clinical data. Standardized preanalytical saliva handing and analytically validated assays will provide accurate and reliable biomarker data. Prototype device will show technical feasibility of the commercial test. Overall, this project has a high potential for a wide-ranging impact on clinical AD care by providing an objective, noninvasive and clinically feasible biological biomarker for diagnosis of AD and MCI, and translating this innovation into a standardized, scalable and cost-effective point- of-care (POC) test for routine dementia screening in the general population. The proposed product has a strong commercial potential based on a proven and low risk LFA device with known and achievable FDA path, competitive patent portfolio, limited competition and key opinion leaders committed to clinical adoption.

Public Health Relevance Statement:
PROJECT NARRATIVE Rapid saliva test for noninvasive diagnostic screening of MCI and dementia This project will develop a new device, a rapid saliva test for diagnostic screening of Alzheimer's disease and its early stage, the Mild Cognitive Impairment (MCI). The new test will provide increased access, acceptability and deliverability of early dementia diagnosis in community settings aiming to delay disease progression, extend the healthy, active years of life and save costs.

Project Terms:
Accounting; Adoption; ages; Age; advanced age; elders; geriatric; late life; later life; older adult; older person; senior citizen; Elderly; AD dementia; Alzheimer Type Dementia; Alzheimer disease dementia; Alzheimer sclerosis; Alzheimer syndrome; Alzheimer's; Alzheimers Dementia; Primary Senile Degenerative Dementia; primary degenerative dementia; senile dementia of the Alzheimer type; Alzheimer's Disease; Biological Assay; Assay; Bioassay; Biologic Assays; Buffers; Classification; Systematics; Cohort Studies; Concurrent Studies; Diagnosis; Disease; Disorder; Education; Educational aspects; Female; Geography; Goals; Health; Health Services Accessibility; Access to Care; access to health services; access to services; access to treatment; accessibility to health services; availability of services; care access; health service access; health services availability; service availability; treatment access; Human; Modern Man; Immunoassay; male; Methods; Statistical Models; Probabilistic Models; Probability Models; statistical linear mixed models; statistical linear models; United States National Institutes of Health; NIH; National Institutes of Health; Neuropsychology; Neuropsychologies; neuropsychologic; Legal patent; Patents; Race; Races; racial; racial background; racial origin; Risk; Saliva; Sensitivity and Specificity; Specificity; Standardization; Technology; Testing; Translating; rho; Measures; Cost Savings; Health Costs; Healthcare Costs; Health Care Costs; Diagnostic tests; Normal Values; Normal Range; Disease Costs; Sickness Cost; Cost of Illness; Guidelines; human subject; Lateral; Site; Chronic; Clinical; Phase; biologic; Biological; Evaluation; Training; Sample Size; Disease Progression; non-invasive diagnosis; non-invasive diagnostic; noninvasive diagnostic; noninvasive diagnosis; Diagnostic; Specimen; Research Specimen; Life; Dementia; Amentia; Neurocognitive; Services; American; Early Diagnosis; early detection; Performance; diagnostic accuracy; Accuracy of Diagnosis; cohort; Participant; economic cost; General Population; General Public; Devices; Modeling; Sampling; response; Dose; Data; Clinical Data; Cognitive; Enrollment; enroll; Small Business Innovation Research Grant; SBIR; Small Business Innovation Research; Validation; validations; Characteristics; sex; point of care; Pathway interactions; pathway; disease phenotype; saliva assay; saliva based assay; saliva based test; saliva test; salivary test; salivary assay; cost; burden of disease; disease burden; years of life lost to disability; years of life lost to disease; burden of illness; digital; designing; design; Outcome; cost effective; innovate; innovative; innovation; early therapy; Early treatment; Alzheimer screening; Alzheimer disease screening; demographics; prototype; clinical care; community setting; candidate biomarker; candidate marker; bio-markers; biologic marker; biomarker; Biological Markers; phase II study; phase 2 study; screenings; screening; mild cognitive disorder; mild cognitive impairment; diagnostic marker; diagnostic biomarker; biomarker selection; diagnostic screening; marker validation; biomarker validation; Alzheimer's biomarker; Alzheimer's disease biological marker; Alzheimer's biological marker; Alzheimer's disease biomarker; statistical and machine learning; machine learning based method; machine learning methodologies; machine learning method; Alzheimer's diagnosis; Alzheimer's disease diagnosis; Alzheimer's care; Alzheimer's disease care; salivary sample; saliva sample; lateral flow test; lateral flow assay; point of care testing