PRINCETON, NJ, United States
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Described are methods for detection of neuronal pathologies using quantitative analysis in bodily fluids of synapse and/or neurite small RNAs and application of these methods to early diagnosis and monitoring of neurodegenerative diseases and other neurological disorders.


Patent
Diamir, Llc | Date: 2017-02-22

Described are methods for early noninvasive or minimally invasive detection of pathological changes in organ systems/organs/tissues/cells by quantifying organ system-/organ-/tissue-/cells type-enriched miRNA in bodily fluids.


Described are methods for early diagnosis and progression monitoring of Mild Cognitive Impairment (MCI) and Alzheimers Disease (AD) by quantifying neurite and/or synapse miRNAs in bodily fluids.


Grant
Agency: Department of Health and Human Services | Branch: National Institutes of Health | Program: SBIR | Phase: Phase II | Award Amount: 1.50M | Year: 2015

DESCRIPTION provided by applicant Alzheimerandapos s disease AD is the most common neurodegenerative disease ND Currently in the US there are M AD patients associated healthcare cost is $ B per year of people age have Mild Cognitive Impairment MCI of which estimated progress to dementia annually Although no disease modifying therapy for AD is available stratified analysis of data from recent clinical trials revealed promising results for early stage patients Thus there is a great need for accurate noninvasive cost effective diagnostics for primary screening DiamiR develops innovative tests for early detection and monitoring of AD and other NDs based on analysis of brain enriched microRNAs miRNAs circulating in plasma Recently we identified and validated a biomarker signature of miRNA pairs andquot miR andquot and andquot miR andquot families capable of differentiating MCI from age matched control with up to accuracy In the SBIR Phase I study several additional miRNA pairs have shown promise for prediction of MCI to AD transition and differentiation of MCI and AD from Parkinsonandapos s disease PD The present SBIR Phase II study aims to test candidate miRNA biomarkers identified at DiamiR in plasma samples from larger well characterized heterogeneous cohorts of patients from both prospective and retrospective studies so as to validate biomarker miRNA signatures for early specific detection of AD Specific aims include determining how early MCI and AD can be detected and whether progression from pre MCI and MCI to AD can be reliably predicted assessing correlation of the miRNA biomarkers with existing biomarkers of AD neuroimaging and cerebrospinal fluid biomarkers and validation of biomarker miRNA signatures for differentiation of AD from other NDs PD Frontotemporal Lobe Dementia FTLD and Amyotrophic Lateral Sclerosis ALS The hypothesis underlying DiamiRandapos s approach to biomarker discovery is as follows since early stages of NDs are characterized by neurite and synapse destruction in distinct brain areas and neuron types we hypothesize that miRNA biomarkers for detection of early stages of AD prediction of pre MCI and MCI progression to dementia and differentiation of AD from other NDs can be defined using biomarker miRNA pairs with each pair consisting of miRNAs which are enriched in brain regions affected by a pathology hippocampus for AD midbrain for PD motor neurons for ALS etc and also present in neurites and synapses and other brain enriched miRNAs present in cells and brain regions not involved in the pathology used as normalizers so as to compensate for factors not re lated to the pathology Additional potentially useful miRNA pairs consist of miRNAs not enriched in the brain but involved in the processes characteristic of progressive disease stages e g inflammation apoptosis and of brain enriched miRNAs Lab Developed Tests LDTs based on the miRNA signatures validated herein will be developed under CLIA guidelines and used to screen patients for clinical trials The tests will assist researchers and clinicians with detecting MCI and predicting whether MCI will progress to AD or other NDs PUBLIC HEALTH RELEVANCE In this Phase II SBIR DiamiR plans to examine blood samples from a large number of patients to confirm the utility of novel blood based biomarkers for early specific detection of Alzheimerandapos s disease The biomarkers previously identified at DiamiR are pairs of certain microRNA molecules which are present in different regions of the brain and are also detectable in blood Diagnostic tests based on the validated biomarkers will be used to screen asymptomatic and early stage patients for clinical trials aimed at prevention of Alzheimerandapos s dementia


Described are methods for detection of neuronal pathologies using quantitative analysis in bodily fluids of synapse and/or neurite small RNAs and application of these methods to early diagnosis and monitoring of neurodegenerative diseases and other neurological disorders.


Described are methods for early diagnosis and progression monitoring of Mild Cognitive Impairment (MCI) and Alzheimers Disease (AD) by quantifying neurite and/or synapse miRNAs in bodily fluids.


The invention is directed to methods for early diagnosis, progression and treatment monitoring of Parkinsons disease (PD) and its differentiation from other neurodegenerative diseases by quantifying brain-enriched miRNA in bodily fluids.


Patent
Diamir, Llc | Date: 2012-04-18

Described are methods for early noninvasive or minimally invasive detection of pathological changes in organ systems/organs/tissues/cells by quantifying organ system-/organ-/tissue-/cells type-enriched miRNA in bodily fluids.


Grant
Agency: Department of Health and Human Services | Branch: | Program: SBIR | Phase: Phase I | Award Amount: 223.59K | Year: 2013

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


Grant
Agency: Department of Health and Human Services | Branch: National Institutes of Health | Program: SBIR | Phase: Phase I | Award Amount: 224.61K | Year: 2016

DESCRIPTION provided by applicant A number of academic groups and life sciences companies are developing and testing approaches to delay aging the most significant risk factor for the vast majority of serious human diseases Critical for these efforts is the development and validation of minimally invasive cost effective biomarkers of aging DiamiR a molecular diagnostics company has developed proprietary platform technology for early detection and moni toring of pathophysiological processes in different organs based on analysis of organ enriched microRNA miRNA pairs in plasma In this SBIR Phase I we propose to use the technology to select effective biomarkers of brain aging Brain aging is characterized by neurite and synapse dysfunction and loss and neuronal death A hypothesis being tested in the current proposal is that these processes can be detected in vitro by quantitative RT qPCR analysis of brain enriched and inflammation associated miRNAs circulating in the blood miRNAs enriched in different brain regions hippocampus midbrain cerebellum cortex pituitary gland and present in neurites and synapses and several inflammation associated miRNAs will be tested as biomarker candidates Our previous studies on brain health produced highly promising results biomarker miRNA pairs selected among brain enriched miRNAs circulating in plasma were found to detect Mild Cognitive Impairment MCI with up to accuracy predict progression from normal cognition to MCI with accuracy years prior to clinical diagnosis and differentiate Alzheimerandapos s and Parkinsonandapos s diseases from age matched control and from each other with accuracy andgt In the preliminary study on aging several brain enriched miRNAs were found to differentiate cognitively normal subjects of two age groups with p andlt to p andlt The current study will be performed using plasma samples prospectively collected at the New York Blood Center Specific aims include assessing feasibility of the approach and selecting miRNA biomarker pairs effectively differentiating younger year old from older year old healthy subjects samples per group and using sets of miRNA biomarker pairs selected in Aim to evaluate age related dynamics and gender dependent differences in plasma samples collected from to year old healthy subjects samples in total In Phase II DiamiR will assemble a knowledgebase by conducting studies with plasma samples collected from to year old subjects Further miRNAs enriched in other than brain organs will be tested as biomarkers of aging of these organs The generated data will be used to determine age dependent ranges of concentrations of miRNA biomarker pairs defining normal aging The long term goal of the project is to develop sensitive minimally invasive molecular assays for evaluation and monitoring of aging in the brain and other organs The assays will be developed as in vitro diagnostics IVD and used for monitoring of aging for assessment of therapeutic regimens and life style changes aimed at delaying or reversing normal aging and for early detection of anomalies characteristic of aging associated diseases PUBLIC HEALTH RELEVANCE Aging is the most significant risk factor for the vast majority of serious human diseases Critical for the efforts to delay aging and increase longevity is the development of effective biomarkers of aging Building on its prior success in studies on brain health biomarkers in this SBIR DiamiR is developing an assay for monitoring brain aging based on quantitative analysis of brain enriched and inflammation associated microRNAs in plasma

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