A Chemiluminescent Assay and Device for Monitoring Vascular Endogenous Nitric Oxide This STTR Phase I project aims to establish the feasibility of a novel chemiluminescent assay for the detection of nitric oxide in blood. Phase II will aim to use this assay in a point-of-care device to measure vascular endogenous nitric oxide (VeNO) from a finger-prick of blood for ultimate deployment in a clinical setting. Vascular nitric oxide is fundamental to cardiovascular health and an accurate measure will streamline drug discovery efforts, help monitor patients, and identify patients that are most likely to benefit from therapies that target nitric oxide signaling. This proposal is a collaboration between BioLum Sciences, LLC and the PIs laboratory at Southern Methodist University. The specific aims include: Aim 1 (BioLum) Optimize and validate a chemiluminescent assay for sensitive and specific nitric oxide measurement in blood Preliminary data has demonstrated the ability of a novel chemiluminescent assay to measure nitric oxide in aqueous buffers. This assay uses the chemiluminescent spiroadamantane 1,2-dioxetane reagent, PNCL, to measure peroxynitrite formed by trapping nitric oxide with superoxide. Using funding from this award, BioLum will optimize this assay for increased sensitivity, characterize its efficacy for measuring nitric oxide in blood samples, and validate the assay with contemporary nitric oxide measurement methods. Aim 2 (SMU) Measure and optimize NO decomposition kinetics under assay conditions Measurement of vascular endogenous nitric oxide in a finger-prick of blood will depend on the decomposition kinetics upon separation from a source of production. These kinetics will be measured using solid-supported nitric oxide donors and stopped-flow spectroscopy techniques. The decomposition rate in aerated buffer in the absence and presence of red blood cells will be determined and assay conditions will be formulated for optimal nitric oxide lifetimes. Public Health Relevance Statement Project Narrative Vascular endogenous nitric oxide (VeNO) is a gas that the cardiovascular system uses to regulate blood pressure and promote healthy function, but VeNO levels are misregulated in many diseases including heart disease, hypertension, erectile dysfunction, and stroke. Many classes of medicines targeting VeNO signaling are available, for example nitroglycerin, Viagra, and Adempas, but identifying which of these medicines will most improve a patients health remains challenging. The aim of this project is to develop a point-of-care device to monitor VeNO to help patients with cardiovascular disease manage their condition and help clinicians personalize treatment to improve patient outcomes.
Project Terms: Award ; Biological Assay ; Assay ; Bioassay ; Biologic Assays ; Biomedical Research ; Blood ; Blood Reticuloendothelial System ; Blood Vessels ; vascular ; Buffers ; Cardiovascular Diseases ; cardiovascular disorder ; Cardiovascular system ; Cardiovascular ; Cardiovascular Body System ; Cardiovascular Organ System ; Heart Vascular ; circulatory system ; Cardiovascular Physiology ; cardiovascular function ; Cause of Death ; Disease ; Disorder ; Drug Industry ; Pharmaceutic Industry ; Pharmaceutical Industry ; Pharmaceutical Preparations ; Drugs ; Medication ; Pharmaceutic Preparations ; drug/agent ; Erythrocytes ; Blood erythrocyte ; Erythrocytic ; Marrow erythrocyte ; Red Blood Cells ; Red Cell ; blood corpuscles ; Fingers ; Gases ; Nitroglycerin ; Glyceryl Trinitrate ; trinitrate 1,2,3-Propanetriol ; Health ; Heart Diseases ; Cardiac Diseases ; Cardiac Disorders ; heart disorder ; Heart failure ; cardiac failure ; Hypertension ; Vascular Hypertensive Disease ; Vascular Hypertensive Disorder ; high blood pressure ; hyperpiesia ; hyperpiesis ; hypertensive disease ; Kinetics ; Laboratories ; Medicine ; Methods ; United States National Institutes of Health ; NIH ; National Institutes of Health ; Nitric Oxide ; Endogenous Nitrate Vasodilator ; Endothelium-Derived Nitric Oxide ; Mononitrogen Monoxide ; Nitrogen Monoxide ; Nitrogen Protoxide ; endothelial cell derived relaxing factor ; oxidation ; Patient Monitoring ; Patients ; Production ; Reagent ; Science ; Signal Transduction ; Cell Communication and Signaling ; Cell Signaling ; Intracellular Communication and Signaling ; Signal Transduction Systems ; Signaling ; biological signal transduction ; Spectrum Analysis ; Spectroscopy ; Spectrum Analyses ; Stroke ; Apoplexy ; Brain Vascular Accident ; Cerebral Stroke ; Cerebrovascular Apoplexy ; Cerebrovascular Stroke ; brain attack ; cerebral vascular accident ; cerebrovascular accident ; Superoxides ; Superoxide Anion ; Superoxide Radical ; Universities ; Generations ; Measures ; Peroxonitrite ; peroxynitrite ; Blood specimen ; Blood Sample ; improved ; Chemiluminescence assay ; Chemiluminescence Measurements ; Chemiluminescent Assays ; Chemiluminescent Measurements ; Chemoluminescence Measurements ; Solid ; Clinical ; Phase ; Erectile dysfunction ; Measurement ; Funding ; Collaborations ; Letters ; Therapeutic ; Methodists ; Methodist Church ; Disorder Management ; Disease Management ; Source ; Techniques ; interest ; empowered ; biocompatibility ; biomaterial compatibility ; monitoring device ; aqueous ; Nitric Oxide Donors ; Viagra ; BP control ; BP homeostasis ; BP management ; BP regulation ; blood pressure control ; blood pressure homeostasis ; blood pressure management ; regulate BP ; regulate blood pressure ; blood pressure regulation ; novel ; Basic Research ; Basic Science ; Prevention ; Devices ; Pathogenesis ; Early identification ; Sampling ; drug development ; drug discovery ; Pharmaceutical Agent ; Pharmaceuticals ; Pharmacological Substance ; Pharmacologic Substance ; Address ; Data ; Detection ; Nitric Oxide Signaling Pathway ; Patient-Focused Outcomes ; Patient outcome ; Patient-Centered Outcomes ; Small Business Technology Transfer Research ; STTR ; Monitor ; Development ; developmental ; point of care ; cost ; Outcome ; Coupled ; comparative ; new therapeutic target ; new drug target ; new druggable target ; new pharmacotherapy target ; new therapy target ; novel drug target ; novel druggable target ; novel pharmacotherapy target ; novel therapeutic target ; novel therapy target ; standard measure ; personalized medicine ; personalization of treatment ; personalized therapy ; personalized treatment ; targeted treatment ; targeted drug therapy ; targeted drug treatments ; targeted therapeutic ; targeted therapeutic agents ; targeted therapy ; cardiovascular health ; Formulation ; clinical translation ; detection assay ; detection limit ;
