Serum Hepcidin Immunoassay: Laboratory to Marketplace

描述(申请人提供)：铁代谢障碍是最常见的人类疾病之一。在过去的十年里，对铁稳态及其紊乱的分子基础的了解取得了迅速的进展。多肽荷尔蒙海普西丁已成为铁代谢的主要调节剂。海普西丁的失调是大多数全身性铁紊乱的主要或致病因素。有一个公认的尚未得到满足的需求，即一种强大的和广泛可用的血清庚西丁临床检测方法，但由于庚西丁的免疫原性较差，这一目标的进展已经放缓。内在生命科学(ILS)开发并验证了世界上第一个依赖于有限供应的高质量兔多克隆抗体的血清海普西丁免疫分析(竞争ELISA)。为了提高海普西丁的可获得性和标准化，利用第一阶段SBIR资金，制备了抗海普西丁的鼠源性单抗。在该方案的第二阶段中，我们将：1)使用单抗优化和验证第二代改进的竞争ELISA检测海普西丁；2)生产更多的抗海普西丁的单抗，并建立和验证双抗夹心ELISA。第二阶段的成功完成将使ILS能够提供一种适合FDA批准并被临床医生和研究人员广泛采用的海普西丁免疫分析原型。 公共卫生相关性：在SBIR第二阶段的资助下，内在生命科学(ILS)将开发第一个适用于FDA批准的铁调节激素海普西丁的原型诊断测试。对海普西丁的测量将极大地改善对普遍存在的遗传性和获得性铁紊乱以及与炎症性疾病和癌症相关的贫血的诊断。

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.