Serum Hepcidin Immunoassay: Laboratory to Marketplace

描述（申请人提供）：铁代谢紊乱是人类最常见的疾病之一。近十年来，对铁稳态及其失调的分子基础的认识取得了快速进展。肽激素hepcidin已成为铁代谢的主要调节因子。hepcidin的失调是大多数系统性铁紊乱的主要或促成因素。对于血清hepcidin的一种强大的、广泛可用的临床检测方法的需求是公认的，但由于hepcidin的免疫原性较差，这一目标的进展已被减缓。Intrinsic Life Sciences （ILS）开发并验证了世界上第一个血清hepcidin免疫测定（竞争性ELISA），该方法依赖于有限供应的高质量兔多克隆抗体。为了提高hepcidin ELISA的可获得性和标准化，利用SBIR I期资金生产hepcidin的小鼠单克隆抗体。在第二阶段，我们将：1)使用单克隆抗体来优化和验证hepcidin的第二代改进竞争性ELISA； 2)生产额外的hepcidin单克隆抗体，并开发和验证双单克隆抗体夹心ELISA。II期的成功完成将使ILS能够提供适合FDA批准的hepcidin免疫测定原型，并被临床医生和研究人员广泛采用。

DESCRIPTION (provided by applicant): Disorders of iron metabolism are among the most common human diseases. During the last decade, rapid progress has been made in the understanding of the molecular basis or iron homeostasis and its disorders. The peptide hormone hepcidin has emerged as the master regulator of iron metabolism. Dysregulation of hepcidin is the principal or contributing factor in most systemic iron disorders. There is a well recognized unmet need for a robust and widely available clinical assay for serum hepcidin but progress towards this goal has been slowed by the poor immunogenicity of hepcidin. Intrinsic Life Sciences (ILS) developed and validated the world's first serum hepcidin immunoassay (competitive ELISA), that relied on a finite supply of high quality rabbit polyclonal antibodies. In order to increase the availability and standardization of the hepcidin ELISA, Phase I SBIR funding was used to produce murine monoclonal antibodies against hepcidin. Under Phase II of this proposal we will: 1) Use the monoclonal antibodies to optimize and validate a 2nd generation improved competitive ELISA for hepcidin 2) Produce additional monoclonal antibodies to hepcidin and develop and validate a two-monoclonal antibody sandwich ELISA. Successful completion of Phase II will enable ILS to deliver a hepcidin immunoassay prototype suitable for FDA approval and widespread adoption by clinicians and researchers. PUBLIC HEALTH RELEVANCE: With Phase II SBIR funding, Intrinsic Life Sciences (ILS) will develop the first prototype diagnostic tests suitable for FDA-approval for the iron-regulating hormone hepcidin. Measurement of hepcidin will permit greatly improved diagnosis of prevalent genetic and acquired iron disorders and anemias associated with inflammatory diseases and cancers.