Brain Natriuretic Peptides - Diagnostic Application

Mischak, Ronald

Abstract

Brain Natriuretic Peptide (BNP) is a cardiac-derived peptide hormone with potent cardiovascular and renal actions. Elevated plasma levels of BNP and its precursor pro-BNP correlate with ventricular hypertrophy and severity of cardiac dysfunction. Commercial radioimmunoassays for BNP are expensive, complex and require plasma extraction before assay. Assays for pro-BNP are not available. We developed a sensitive ELISA for BNP and found dramatically elevated BNP levels in patients with severe Congestive Heart Failure. BNP levels correlated directly with pulmonary capillary wedge pressure (PCWP) and inversely with the left ventricular ejection fraction (EF) which are objective measures of cardiac function. Recent reports suggest that pro-BNP or the pro-BNP/BNP ratio may provide a more sensitive indicator of cardiac dysfunction. In Phase I we will develop an ELISA assay for pro-BNP and compare pro-BNP and BNP levels in existing human plasma samples. Values for pro-BNP, BNP, and the pro-BNP/BNP ratio will be compared to clinical parameters such as CArdiac index (CI), (EF), (PCWP) and other indices of disease severity. Phase II studies will involve testing samples from patients with mild through severe cardiac dysfunction to establish assay sensitivity, specificity and overall acceptability in measuring severity of dysfunction.

Proposed Commercial Applications

Brain Natriuretic Peptide (BNP) and its precursor form (proBNP) are markedly elevated in patients with certain cardiovascular disorders. A direct correlation between plasma levels of BNP peptides and disease severity provides the basis for a screening test for cardiac dysfunction. This test would have significant value in the diagnosis, staging and treatment of cardiovascular disease.