Development of the Novel Small molecule drug Posiphen to treat Traumatic Brain In

DESCRIPTION (provided by applicant): Alzheimer's Disease (AD) is the most common neurodegenerative disease: 5.4 million people are currently living with AD in the US, and up to 80 million Americans (over 55 years old) are considered to constitute the riskgroup for AD. In 2011, the annual cost of healthcare services for AD patients in the US reached 183 billion. There are currently no disease-modifying therapies available to AD patients, and the development of new therapeutics is complicated in large partby the absence of effective methods for early diagnosis and monitoring of the disease. In this SBIR DiamiR proposes to develop a cost-effective minimally invasive test for early specific detection of AD and prediction of disease progression from Mild Cognitive Impairment (MCI) to AD dementia. The test will be based on RT-PCR analysis of cell-free miRNA in plasma - a simple assay, which can be performed in most clinical labs. The test will potentially be used (1) to identify patients in earl, reversible stages of the disease that can be recruited for clinical trials, (2) to monitor patients response to various treatments, and (3) to better plan clinical care in earlier stages of the disease. Early stages of AD are characterized by neurite and synapse destruction in hippocampus and cortex. DiamiR hypothesizes that the following innovations will allow highly sensitive detection of these processes in vitro using quantitative analysis of cell-free miRNA in plasma: (1) brain-enriched miRNA present in neurites and synapses of hippocampus will be tested as potential biomarkers, and (2) concentrations of biomarker miRNA will be normalized per other brain-enriched miRNA, located in cells and brain areas not involved in the pathology, so as to compensate for factors notrelated to AD yet affecting concentrations of biomarker miRNA in plasma. DiamiR's preliminary studies have been highly promising: measurement of plasma concentrations of several biomarker and normalizer miRNA, selected as just described, allowed differentiating MCI from the age- matched control with both sensitivity and specificity gt85%, exceeding the targets specified by the Alzheimer's Association. The present Phase I study addresses feasibility of early specific detection of AD in MCI patients. The Phase I specific aims are: (1) assess feasibility of detecting MCI patients that will progress to the AD dementia; and (2) demonstrate that using miRNA enriched in certain brain areas allows for effective differentiation between distinct neurodegenerative diseases. As Phase II, DiamiR will conduct a large longitudinal study designed to validate the biomarker/normalizer sets identified in preliminary studies (early MCI detection) and Phase I, and to test the utility of these sets for detecting MCI in asymptomatic subjects, as well as for predicting and monitoring MCI to AD dementia transition. All data analysis will be performed using custom-built computer program developed at DiamiR. As the project matures, DiamiR will explore partnering with a larger diagnostics firm to bring the test to market, and with pharmaceutical companies to explore use of the technology for patient stratification and as companion diagnostics. PUBLIC HEALTH RELEVANCE PUBLIC HEALTH RELEVANCE: Patients afflicted with Mild Cognitive Impairment (MCI) may revert to normal status, remain in MCI condition for a prolonged period of time, or progress to various dementias. In this SBIR DiamiR is developing a cost- effective non-invasive test to identify MCI patients likely to develop Alzheimer's dementia. The test, which is based on analysis of brain-enriched miRNA in plasma, will help select patients for clinical trials, assess patients' response to different treatments, and plan clinical care in earlier stages of the disease