Brain-enriched microRNAs detectable in plasma as biomarkers of Alzheimer's Disease

SUMMARY One in 10 Americans aged 65 and older have Alzheimer’s disease (AD). Since AD begins with a prolonged, over 10 year-long, asymptomatic stage, a growing number of companies are developing new therapies that aim to intervene early in the progression of AD and related forms of dementia. There is thus a great need for minimally invasive diagnostic tools for primary screening of individuals with early stages of the disease. DiamiR has developed a platform technology for detection, prognosis, and monitoring of different stages (from the preclinical stage to dementia) of AD based on targeted selection and analysis of brain-enriched and inflammation- associated microRNAs (miRNAs) circulating in blood plasma. Working with leading academic Alzheimer’s Disease Centers, DiamiR has produced a large amount of data, which supports the use of miRNA biomarkers for detection of AD at different stages of the disease. This data include detection of clinically diagnosed mild cognitive impairment (MCI) with accuracy of 95%, differentiation of AD from other neurodegenerative diseases with ≥80% accuracy, and identification of cognitively normal subjects who would later progress to MCI with 75% accuracy. Based on an analysis of over 1,000 well-characterized plasma samples, we defined 24 miRNAs for a diagnostic test, CogniMIRTM. The objective of the current Commercialization Readiness Program (CRP) is to develop a clinic-ready lab-developed test (LDT) compliant with Clinical Laboratory Improvement Amendments (CLIA) guidelines for detection of preclinical AD, MCI, and AD. In the ongoing Phase IIB study, we worked with the Roskamp Institute and Thermo Fisher Scientific to analyze multiple pre-analytical factors in order to minimize variability and increase sensitivity and reproducibility of the assay. We optimized the protocol for blood collection, plasma preparation, and miRNA extraction. Further, we have developed a detailed workflow for the analysis of 24-miRNA classifier. In the present CRP project, in partnership with Interpace Biosciences we will finalize assay protocol for the clinical setting and implement the test in a CLIA-compliant laboratory. Following analytical validation, we will perform a multi-center double-blinded cross-sectional clinical study to assess test performance for detection of preclinical AD, MCI, and AD among representative elderly subjects seen at geographically diverse Alzheimer’s Disease Centers in the US. Provided the project is successful, the new LDT comprising CogniMIRTM could be immediately used to help screen patients for MCI/AD clinical trials. Once the CogniMIRTM test is validated with 15,000-20,000 patient samples from heterogeneous cohorts, we will broadly launch the test to gerontologists/neurologists and other medical professionals engaged in AD treatment and care.