Assay for Monitoring Glycemic Control in Diabetics

描述（由申请人提供）：目前全世界有超过1亿人患有糖尿病，其中美国有近1800万人患有糖尿病。在美国，这种疾病及其相关并发症被列为第七大死因。为了显著改善糖尿病管理，迫切需要诊断来评估糖尿病患者对各种治疗方法的依从性，特别是对强化胰岛素治疗的依从性（例如，通过胰岛素注射、泵使用或在不久的将来通过实施闭环系统）。BioTex的研究人员建议开发一种价格合理的诊断试剂盒，用于对糖尿病患者1-6周的血糖控制情况进行回顾性评估。BioTex的创新检测将同时针对血清中的几种糖基化产物，其与葡萄糖的非酶缩合反应程度与血液中的平均葡萄糖水平相关。由于糖化蛋白靶标具有不同的生命周期，因此该分析不仅可以提供一个时间框架的平均葡萄糖水平，还可以提供过去6周内5个不同时间框架的平均葡萄糖水平。一次性诊断试剂盒的创新元素将是使用适配体（短寡核苷酸）与蛋白质目标特异性结合，以及用于荧光检测的量子点。为了完成这项任务，在第一阶段，我们将通过选择五种糖化蛋白（如血红蛋白HbA1c、IgM、IgG、血清白蛋白和纤维蛋白原）特异性适配体进行概念验证，然后使用微孔板阅读器进行荧光检测。适配体将通过SELEX协议（配体的系统进化通过指数富集）从随机文库中选择，这将使我们能够筛选配体到选定数量的突出糖化蛋白（仅在几天内以自动和合理的方式）。与抗体形成鲜明对比的是，适体的生产成本要低得多，可重复性也高得多。BioTex的研究人员相信，这种新方法如果成功，可以显著提高回顾性血糖控制监测的临床相关性，特别是评估闭环系统的临床有效性。

DESCRIPTION (provided by applicant): Diabetes is currently believed to afflict over 100 million people worldwide and nearly 18 million in the United States. In the U.S. this disorder, along with its associated complications, is ranked as the seventh leading cause of death. To significantly improve diabetes management, there is an urgent need for diagnostics to assess compliance to of diabetics to various treatment methods, and, in particular, to intensive insulin therapy (e.g. by insulin injection, pump use, or by the implementation of a closed loop system in the near future). BioTex researchers propose to develop an affordable diagnostic kit for retrospective assessment of glycemic control in diabetics over a preceding time frame of 1-6 weeks. BioTex' innovative assay will simultaneously targets several glycation products in serum, whose degree in non-enzymatic condensation reaction with glucose correlates with the mean glucose level in blood. Since the glycated protein targets will have different life times, the assay will provide the mean glucose level not only for one time frame, but 5 different time frames within the past 6 weeks. The innovative element of the the disposable diagnostic kit will be the use aptamers - short oligonucleotides - for specific binding to the protein targets, and quantum dots for fluorescence detection. To accomplish this task, in Phase I we will perform proof-of- concept by selecting aptamers specific to five glycated proteins (e.g. hemoglobin HbA1c, IgM, IgG, serum albumin, and fibrinogen), followed by fluorescence detection using a microplate reader. Aptamers will be selected from random libraries by SELEX protocol (Systematic Evolution of Ligands by Exponential enrichment) that will allow us to screen ligands to a selected number of prominent glycated proteins (in an automated and rational way within a few days only). In stark contrast to antibodies, aptamers are much more affordable to produce with much better reproducibility. BioTex researchers are confident that this novel approach, if successful, can significantly enhance the clinical relevance of retrospective monitoring of glycemic control, especially for assessing clinical effectiveness of a closed loop system. PUBLIC HEALTH RELEVANCE: There is an urgent need for diagnostics to assess compliance to various treatment methods of diabetes, and, in particular, intensive insulin therapy (e.g. by using insulin pumps, or an artificial beta cell in the near future). Diabetes is currently believed to afflict over 100 million people worldwide and nearly 18 million in the United States. In the U.S. this disorder, along with its associated complications, is ranked as the seventh leading cause of death. BioTex proposes to develop a innovative diagnostic kit for assessing compliance of diabetics, who undergo intensive insulin therapy. Compliance will be assessed by retrospective evaluation of glycemic control (mean glucose level) over the preceding 6-8 weeks (1-6 weeks) within different time windows. The clinical utility of this kit will allow the clinician to make more meaningful decisions about adjustments of insulin therapy, life-style, or diet.