Non-radioactive Multiplexed Assays for Prediction/Diagnosis of T1D and Comorbid A

用于预测/诊断 T1D 和合并症 A 的非放射性多重检测

• 批准号: 8402752
• 负责人: Anu Mathew
• 金额: $ 29.56万
• 依托单位: MESO SCALE DIAGNOSTICS, LLC
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-09-01 至 2014-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8402752
• 关键词: Acute; Addison' s disease; Affect; Affinity; Algorithms; Antibodies; Antigens; Autoantibodies; Autoantigens; Autoimmune Diseases; Autoimmune Process; Autoimmune Responses; Biological Assay; Biological Markers; Blinded; Blood Tests; Blood specimen; Carboxy-Lyases; Celiac Disease; Centers for Disease Control and Prevention (U.S.); Child; Childhood; Collaborations; Comparative Study; Detection; Development; Diabetes Mellitus; Diabetes prevention; Diagnosis; Diagnostic; Diagnostic tests; Disease; Disease Progression; Goals; High Prevalence; Immobilization; Immune response; Incidence; Insulin; Insulin-Dependent Diabetes Mellitus; International; Iodide Peroxidase; K ATPase; Label; Laboratories; Liquid substance; Measures; Methods; Monitor; Patients; Performance; Phase; Plasma; Population; Prevention therapy; Process; Production; Proinsulin; Proteins; Protocols documentation; Qualifying; Radioactive; Radioactive Waste; Radioactivity; Radioimmunoassay; Reproducibility; Risk; Sampling; Screening procedure; Sensitivity and Specificity; Serum; Small Business Innovation Research Grant; Specificity; Standardization; Steroid 21-Monooxygenase; Technology; Testing; Therapeutic; Thyroid Diseases; Thyrotropin Receptor; Training; Transglutaminases; Validation; Waste Management; assay development; base; clinical practice; cohort; cost; diabetic; effective therapy; insulin dependent diabetes mellitus onset; pediatrician; point of care; prevent; programs; young adult

DESCRIPTION (provided by applicant): Type 1 Diabetes (T1D) affects an estimated one in three hundred young people in the U.S., with increasing annual incidence. It is primarily an autoimmune disease and is often associated with other serious autoimmune conditions such as Addison's, celiac, and thyroid diseases. Current diagnostic protocols use radioactivity-based assays, measuring multiple autoimmune markers individually. There is a need for the development of better tests to diagnose/predict who will develop T1D, and for monitoring disease progression and therapeutic responsiveness, especially once effective treatments to prevent or delay T1D become available. The completion of the proposed SBIR project, carried out in collaboration with Drs. Yu and Eisenbarth (Barbara Davis Center for Childhood Diabetes), will result in development of sensitive multiplexed assay panels with required sensitivity and specificity for identification of pre-diabetic or recent onset T1D cases, and detection of associated autoimmune diseases. These panels will use sensitive Meso Scale Diagnostics, LLC. (MSD) MULTI-ARRAY(R) detection technology and will use small volumes of patient blood samples to simultaneously detect multiple autoimmune responses. The arrays will incorporate an MSD(R) technology-based assay for pro-insulin and insulin auto-antibodies (IAA) developed by our collaborators that has been shown to outperform currently used IAA radioimmunoassay in multi-laboratory comparative studies. Following subsequent Phase II and III development, the assay panels will be suitable for widespread use with patient samples, providing high accuracy, reproducibility and throughput at significantly lower costs than current singleplex radioactivity-based methods with their inherent regulatory and radioactive waste management issues. The MSD assay format also lends itself to development of point of care assays, making the screening of large populations possible (e.g. in pediatricians' offices) when therapies for the prevention of diabetes enter clinical practice. PUBLIC HEALTH RELEVANCE: The goal of this project is to develop blood tests that will identify patients (primarily children and young adults) who will develop, or have developed, type 1 diabetes and a number of associated autoimmune diseases. The diagnostic tests developed using MSD's highly sensitive multiplex technology will enable doctors to move away from current approaches that use much larger amounts of patient samples to measure biomarkers individually and involve use of radioactivity.

描述（由申请人提供）：1型糖尿病（T1 D）影响美国估计每三百名年轻人中就有一人，每年的发病率都在增加。它主要是一种自身免疫性疾病，通常与其他严重的自身免疫性疾病如阿狄森氏病、乳糜泻和甲状腺疾病有关。目前的诊断方案使用基于放射性的测定，单独测量多种自身免疫标记物。有必要开发更好的测试来诊断/预测谁将发展T1 D，并监测疾病进展和治疗反应性，特别是一旦有效的治疗方法来预防或延迟T1 D变得可用。与Yu博士和Eisenbarth博士（Barbara Davis儿童糖尿病中心）合作完成的拟议SBIR项目将导致开发具有所需灵敏度和特异性的敏感多重检测面板，用于识别糖尿病前期或近期发病的T1 D病例，并检测相关的自身免疫性疾病。这些面板将使用敏感的Meso Scale Diagnostics，LLC。(MSD)MULTI-ARRAY（R）检测技术，并将使用少量患者血液样本同时检测多种自身免疫反应。该阵列将采用我们的合作者开发的基于MSD（R）技术的胰岛素原和胰岛素自身抗体（IAA）检测方法，该方法在多实验室比较研究中已被证明优于目前使用的IAA放射免疫测定法。在随后的II期和III期开发之后，检测板将适用于患者样本的广泛使用，提供高准确性，重现性和通量，成本显著低于当前基于单重放射性的方法及其固有的监管和放射性废物管理问题。MSD测定形式还适用于护理点测定的开发，使得当用于预防糖尿病的疗法进入临床实践时可以筛查大量人群（例如，在儿科医生办公室中）。 公共卫生相关性：该项目的目标是开发血液检测，以识别将发展或已经发展为1型糖尿病和一些相关自身免疫性疾病的患者（主要是儿童和年轻人）。使用MSD的高灵敏度多重技术开发的诊断测试将使医生能够摆脱目前使用大量患者样本单独测量生物标志物并涉及使用放射性的方法。