MicroRNA-based Diagnostic Biomarker for Pulmonary Hypertension

Abstract Mirna Analytics is proposing to develop a microRNAmiRNAmarker for pulmonary hypertensionThis proposal is focused on the identification of optimal miRNAandapos s to form composite markers that can be measured in the serum plasmaPulmonary hypertensionan excessive increase of the pressure in the pulmonary circulationcan be due to many different reasonsPulmonary hypertension can be a deadly disease and in all cases confers a worse prognosisAside from genetic testing and the measurement of the right heart stress marker B type natriuretic peptidebiomarkers that would identify the molecular or cellular pathobiologic mechanism that identify the cause of pulmonary hypertension are not establishedMirna Analytics is focusing on miRNAs as novel candidate biomarkers because these molecules are stable in serum and plasma samples and are circulating for shortand long distance communication between cellsA biomarker tool that can identify the pathogenesis that causes pulmonary hypertension would significantly improve disease management by facilitating personalized therapyPreliminary studies were conducted with plasma and serum samples that were bio banked from previously conducted studies and de identified by two different pulmonary hypertension centers at the Universities of Heidelberg and ZurichThe studies were focused on the effects of supervised exerciseor nightly oxygen interventionsrespectivelyWe identified miRNA based markers that changed with the intervention and that were correlated with theminute walking distance at baselineBased on these preliminary dataproposed study is designed to test the Phase I HypothesisA microRNA marker from the serum plasma is predictive of clinical improvement in pulmonary hypertension following therapeutic management with exerciseor nightly oxygenand has some overlap with predictors of improvements following therapy with the breathing stabilizerAcetazolamideSpecific Aimis to test our two miRNA markers identified in preliminary studiesmiRp relative to miRaormiRpmiRp relative to spike RNAmiRarespectively on validation sample cohorts from Acetazolamide treated patients from the University of Zurich and a new cohort ofpaired samples from the exercise intervention study at the University of HeidelbergSpecific Aimis to expand our miRNA marker portfolio by testing additionalmiRNA speciesSpecific Aimis to test the RNA fromrandomly selected pairs each from the sample cohorts fromaoxygenor placebo group patients from the University of Zurichand bbefore and after exercise intervention study at the University of Heidelberg with an Omics tool to further develop our miRNA markerThe Commercial Application is to develop a circulating biomarker that supports the $billion PH therapeutic market Public Health Relevance Statement In this Phase I SBIR projectMirna Analytics proposes to develop microRNA based markers for pulmonary hypertensionOur microRNA based biomarker will be measured in the plasma or serumThe biomarker is expected to lead to personalized treatment and prognosis of this deadly disease by helping to determine the cause of pulmonary hypertension