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

描述(申请人提供)：1型糖尿病(T1D)在美国估计每300个年轻人中就有一个受到影响，而且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有关，如爱迪生病、乳糜泻和甲状腺疾病。目前的诊断方案使用基于放射性的分析，分别测量多个自身免疫标志物。需要开发更好的测试来诊断/预测谁会患上T1D，并监测疾病的进展和治疗反应，特别是一旦有了有效的预防或延迟T1D的治疗方法。拟议的SBIR项目是与Yu博士和Eisenbarth博士(Barbara Davis儿童糖尿病中心)合作完成的，该项目将导致开发具有所需灵敏度和特异性的灵敏多重分析小组，以识别糖尿病前期或新近发病的T1D病例，并检测相关的自身免疫性疾病。这些小组将使用敏感的中尺度诊断，有限责任公司。(MSD)多阵列(R)检测技术，将使用少量患者血液样本同时检测多个自身免疫反应。这些阵列将包括由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)分析，在多实验室比较研究中已被证明优于目前使用的IAA放射免疫分析。在随后的第二阶段和第三阶段开发之后，分析板将适用于患者样本的广泛使用，提供高准确度、重复性和吞吐量，成本显著低于目前基于单链放射的方法及其固有的监管和放射性废物管理问题。MSD分析格式还有助于开发护理点分析，使在预防糖尿病的治疗进入临床实践时对大量人群进行筛查成为可能(例如在儿科医生的办公室)。 公共卫生相关性：该项目的目标是开发血液测试，以确定将发展或已经发展为1型糖尿病和一些相关的自身免疫性疾病的患者(主要是儿童和年轻人)。使用MSD的高度敏感的多路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记物并涉及使用放射性的方法。

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.