Development of a novel clinical assay for measuring serum hepcidin levels

开发一种测量血清铁调素水平的新型临床测定方法

• 批准号: 8647340
• 负责人: Shrikumar Ambujakshan Nair
• 金额: $ 27.62万
• 依托单位: AFFINERGY ,INC
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-09-03 至 2015-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8647340
• 关键词: Address; Adoption; Affinity; Amino Acid Sequence; Anemia due to Chronic Disorder; Antibodies; Binding; Biological Assay; Biotinylation; Blood; Blood Cells; Blood Circulation; Clinical; Clinical Management; Complex; Detection; Development; Diagnosis; Disease; Exposure to; FDA approved; Fluorescence Polarization; Goals; Heart Diseases; Hereditary hemochromatosis; Hormones; Hour; Human; Hypoxia; Immunoassay; Infection; Inflammatory; Iron; Iron Metabolism Disorders; Iron Overload; Iron deficiency anemia; Kidney Diseases; Label; Lead; Malignant Neoplasms; Measures; Methods; Monitor; Mono-S; Peptides; Phage Display; Phase; Production; Proteins; Publishing; Scheme; Serum; Solutions; Specificity; Testing; Whole Blood; assay development; base; clinically relevant; cross reactivity; disulfide bond; experience; fluorophore; hepcidin; immunogenicity; iron deficiency; iron metabolism; novel; overexpression; peptide A; peptide hormone; public health relevance; scale up; success

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.

描述（由申请人提供）：铁调素是负责调节循环铁浓度的肽激素。铁调素的过度表达会导致严重的铁缺乏和贫血，而铁调素的缺乏会导致铁过载。毫不奇怪，铁调素产生和循环浓度的异常与各种疾病状态高度相关，例如肾病、癌症、遗传性血色素沉着症（HH）、缺氧、炎症性贫血、感染、炎症性疾病和心脏病。检测血清中铁调素的准确方法将改善我们对铁代谢紊乱的理解、诊断和临床管理。不幸的是，没有 FDA 批准的测定血清中铁调素水平的方法。铁调素的免疫原性非常低，这阻碍了临床相关铁调素测定的发展，这使得生产针对该激素的抗体极具挑战性。现有的少数免疫测定方法在特异性方面的特征很差，并且它们很难将铁调素与循环中发现的多种非活性形式的激素区分开来。 Affinergy 将通过使用噬菌体展示生物淘选来鉴定高度特异性的铁调素结合肽来克服这些问题。基于肽的检测将规避与更传统的免疫检测方法相关的许多挑战和限制，使我们能够加速临床相关铁调素检测的开发，这将解决重大的未满足需求，并具有广泛采用的潜力。