Rapid saliva test for noninvasive diagnostic screening of MCI and dementia

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Project Summary 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.