A point-of-care device for the determination of homocysteine (Hcy), the Hcy Now

Abstract This application pertains to the National Center for Advancing Translational Sciences SBIR/STTR Omnibus Solicitation (preferred). In Vitro Diagnostic Solutions (IVDS) aims to develop a quantitative, home monitoring point-of-care test for determining total blood homocysteine (tHcy) levels which will significantly improve the management of Homocystinurias (HCUs). HCUs are inherited metabolic disorders which lead to the accumulation of plasma Hcy. Classical HCU, the most common disorder, is caused by deficiency in the enzyme known as cystathionine beta-synthase. Additionally, other HCUs (cobalamin (Cbl) disorders C, D, E, F, G, J, K, X, and severe MTHFR are also part of the homocystinuria group) can lead to the accumulation of Hcy. While newborn screening programs in the US test for Classical HCU, not all cases are detected which causes severe irreversible side effects. Early diagnosis and treatment for HCUs avoids the debilitating and deadly side effects of HCUs. High levels of Hcy can result in nearsightedness, developmental and cognitive deficits, seizures, psychiatric disorders, behavior problems, excessive growth of bones, blood clots, coronary artery disease, myocardial infarction, peripheral vascular disease, strokes, and in severe, untreated cases, death. Previously published literature estimated the prevalence of HCU at approximately 1 in 100,000 worldwide. However, a recent study published by the NIH reveals that the actual prevalence of HCU may be 10 times higher (1 in 10,000), and that HCU is not diagnosed until later in life. Current testing for blood Hcy involves a lab visit for a blood draw with test results taking days to weeks. Due to the scarcity of labs capable of measuring Hcy, most patients get tested quarterly or biannually limiting the patient’s ability to effectively manage their Hcy levels through diet and medication. Wide variations in a patient’s Hcy levels and infrequent testing does not provide the full scope of how levels are varying over time. There is an urgent, unmet need for simple-to-use, accurate home monitoring device for tHcy determination to help patients manage their diet and medications. The Hcy Now is cost-effective, portable, and a simple-to-use device for the home monitoring of blood Hcy levels. A mobile app displays and stores results of Hcy concentration Mol/L, which can be remotely disseminated to the care provider to make essential decisions on diet, medications, or if it requires an ER visit. Execution of this platform will shift the clinical paradigm surrounding HCU patient management. The specific aims of this proposal are: 1) Finalize Hcy Detection Formulation, 2) Analytical Validation of Membrane Formulations, 3) Eliminate Hematocrit Bias in the Range of 30% to 52%, 4) Point of Care Mobile Application, 5) Establish Concordance of Hcy Now to the reference analyzer using patient samples.