Novel PhageLock assay to measure hepcidin for clinical monitoring

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SUMMARY/ABSTRACT Hepcidin is the peptide hormone responsible for regulating circulating iron concentrations. Overexpression of hepcidin results in severe iron deficiency and anemia, whereas hepcidin deficiency leads to iron overload. Not surprisingly, abnormalities in hepcidin production and circulating concentrations are highly correlated with various disease states such as renal disease, cancer, hereditary hemochromatosis, hypoxia, anemia of inflammation, infection, inflammatory diseases, and heart disease. Accurate methods for detecting hepcidin in serum will lead to improvements in our understanding, diagnosis, and clinical management of iron metabolism disorders. Unfortunately, there is no FDA-approved assay for measuring hepcidin levels in plasma. The development of a clinically relevant hepcidin assay has been hindered by hepcidin’s very low immunogenicity, making it extremely challenging to produce antibodies against the hormone. The few immunoassays that do exist are poorly characterized in terms of specificity, and they struggle to differentiate hepcidin from the multiple inactive forms of the hormone that are found in the circulation. Affinergy plans to develop a phage-based clinical chemistry assay that will enable frequent, simple, and affordable monitoring of plasma hepcidin-25 levels. Using our core technology of phage display biopanning, we have already identified a proprietary “capture” peptide that binds to hepcidin-25. In this Phase 1 application, we intend to identify a hepcidin-25 specific “detection” phage and incorporate the hepcidin-25-binding peptide and phage in a rapid, easy-to-use sandwich ELISA-based assay. At the conclusion of Phase 1, we expect to have a technology that can be scaled up in Phase 2 for use by clinicians and researchers to measure hepcidin concentrations in plasma.