Differential Capture Proteomics-Diabetes

差异捕获蛋白质组学-糖尿病

• 批准号: 7404666
• 负责人: Paul Stroobant
• 金额: $ 17.5万
• 依托单位: DIFFERENTIAL PROTEOMICS, INC.
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-09-10 至 2010-09-09
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7404666
• 关键词: Affinity; Aliquot; Antigens; Bacteriophages; Binding; Biological; Biological Assay; Biological Markers; Biological Models; Centers for Disease Control and Prevention (U.S.); Cessation of life; Clinical; Diabetes Mellitus; Diagnosis; Disease; Drug Formulations; Epidemic; Generations; Goals; Human; Immobilization; Immunoassay; Knowledge; Laboratories; Lead; Legal patent; Libraries; Mass Spectrum Analysis; Modeling; Monitor; Monoclonal Antibodies; Patients; Peptides; Phage Display; Phase; Phase I Clinical Trials; Phase II Clinical Trials; Plasma; Procedures; Process; Proteins; Proteomics; Range; Reagent; Recurrence; Sampling; Screening procedure; Solid; Specificity; Standards of Weights and Measures; Structure; Technology; Testing; Therapeutic; Time; United States; Validation; Work; assay development; base; cost; health care economics; innovation; member; novel; outcome forecast; programs; success; validation studies

DESCRIPTION (provided by applicant): In the United States in 2002, over 20 million people had diabetes, which contributed to over 224,000 deaths and the total cost of diabetes was $132 billion. A worldwide epidemic of diabetes is now projected which will have serious healthcare and economic consequences. The discovery of new biomarkers will be very important for much-needed advances in screening, diagnosis, prognosis, prediction of disease recurrence and therapeutic monitoring for these devastating diseases. The goal for Phase I of this Project is to optimize in human plasma a new proteomics technology, Differential Capture Proteomics (DCP), which can identify the differences in protein composition between two biological samples. This technology also simultaneously creates affinity reagents for each of the identified difference proteins. A patent for DCP has been issued to Differential Proteomics Inc. The goal for a subsequent Phase II study is to apply DCP, newly optimized for human plasma, to the discovery of biomarkers of diabetes using appropriate patient plasma samples to enable novel protein isolation and identification, novel affinity reagent creation, assay formulation, and clinical validation. Studies in our laboratory to optimize the DCP technology have successfully focused on a model system. However, the capabilities of DCP for diabetes biomarker discovery in patient plasma samples have yet to be demonstrated with an optimization study. Such a study is proposed here, in which doped diabetes biomarkers (representing a model diabetes patient sample) will be tested for detectability at clinical sample level concentrations. The proposed study will use five specific diabetes protein antigens, for which there are commercially available immunoassays. The success of this Phase I study will lead to a Phase II program for testing multiple diabetes patient plasma samples for novel biomarker discovery, assay generation, and validation. Specific Aim 1: Confirm that three pooled Random Peptide Phage Libraries actually contain binding phage species against each of the five diabetes antigens chosen. Specific Aim 2: Show how well Differential Capture Proteomics detects the differences between two human plasma samples, one of which is doped with the mixture of five diabetes antigens. Specific Aim 3: Establish the specificity of the affinity capture reagents that are generated as part of the process.

描述（由申请人提供）：2002年，在美国，超过2000万人患有糖尿病，导致超过224，000人死亡，糖尿病的总成本为1320亿美元。现在预计糖尿病将在全球范围内流行，这将产生严重的医疗保健和经济后果。发现新的生物标志物对于这些毁灭性疾病的筛查、诊断、预后、疾病复发预测和治疗监测方面急需的进展将非常重要。 该项目第一阶段的目标是在人血浆中优化一种新的蛋白质组学技术，即差异捕获蛋白质组学（DCP），该技术可以识别两种生物样品之间蛋白质组成的差异。该技术还同时为每种鉴定的差异蛋白质产生亲和试剂。DCP的专利已颁发给差异蛋白质组学公司。 后续II期研究的目标是将针对人血浆新优化的DCP应用于使用适当的患者血浆样本发现糖尿病生物标志物，以实现新型蛋白质分离和鉴定、新型亲和试剂创建、测定制剂和临床验证。 我们实验室优化DCP技术的研究已经成功地集中在模型系统上。然而，DCP在患者血浆样本中发现糖尿病生物标志物的能力尚未通过优化研究得到证实。本文提出了这样的研究，其中将测试掺杂的糖尿病生物标志物（代表模型糖尿病患者样品）在临床样品水平浓度下的可检测性。拟议的研究将使用五种特定的糖尿病蛋白抗原，这些抗原有市售的免疫测定法。这项I期研究的成功将导致一个II期项目，用于测试多种糖尿病患者血浆样本，以发现新的生物标志物，生成检测试剂盒并进行验证。 具体目标1：确认三个合并的随机肽噬菌体文库实际上含有针对所选五种糖尿病抗原中的每一种的结合噬菌体种类。具体目标二：显示差异捕获蛋白质组学如何检测两个人血浆样本之间的差异，其中一个样本掺杂了五种糖尿病抗原的混合物。具体目标3：确定作为工艺一部分生成的亲和捕获试剂的特异性。