Development of a novel clinical assay for measuring serum hepcidin levels

描述(由申请人提供)：海普西丁是一种负责调节循环铁浓度的多肽激素。海普西丁的过度表达会导致严重的铁缺乏和贫血，而海普西丁的缺乏则会导致铁超载。不足为奇的是，海普西丁的产生和循环浓度的异常与各种疾病状态高度相关，如肾脏疾病、癌症、遗传性血色沉着(HH)、缺氧、炎症贫血、感染、炎症性疾病和心脏病。准确检测血清中海普西丁的方法将有助于提高我们对铁代谢紊乱的认识、诊断和临床处理。不幸的是，目前还没有FDA批准的检测血清中海普西丁水平的方法。由于海普西丁的免疫原性很低，阻碍了临床相关海普西丁试验的发展，这使得生产针对该激素的抗体具有极大的挑战性。现有的少数几种免疫分析方法在特异性方面表现不佳，它们难以区分血液循环中发现的多种不活跃形式的荷尔蒙。AffinEnergy将通过使用噬菌体展示生物扫描来识别高度特异的海普西丁结合肽来克服这些问题。基于多肽的分析将绕过与更传统的免疫分析方法相关的许多挑战和限制，使我们能够加速开发具有临床意义的海普西丁分析，它将解决一个重要的未得到满足的需求，具有广泛采用的潜力。

DESCRIPTION (provided by applicant): 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 (HH), 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 serum. 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 will overcome these problems by using phage display biopanning to identify highly specific hepcidin-binding peptides. A peptide-based assay will circumvent the many challenges and limitations associated with the more traditional immunoassay approach, allowing us to accelerate the development of a clinically relevant hepcidin assay that will address a significant unmet need with the potential for widespread adoption.