Urine glycated CD59 as novel diabetes biomarker amenable to measure with a point-of-care device

项目摘要 糖尿病和糖尿病前期是全世界高度优先的公共卫生问题，因为它们是一个主要原因 成年人的发病率和死亡率都在上升，而且这两者在地球仪范围内都在以流行病的速度增长。 糖尿病和糖尿病前期目前影响世界人口的近9%，据估计， 在今后20年中，全球患病率将增加近50%。Mellitus，LLC正在开发一种新的测试方法， 用于筛查、诊断和监测糖尿病、糖尿病前期和妊娠期糖尿病患者 （GDM）。该测试是基于新的生物标志物糖化CD 59（GCD 59），这是独家许可 来自哈佛大学的Mellitus。该生物标志物的重要特征是：1）它是致病性的， 相关，因为其与糖尿病并发症的发展的机械联系，2）不仅存在 不仅在血液中，而且在尿液和其他体液中，以及3）具有约2周的周转率，这快得多 HbA1c。Mellitus已经开发了一种ELISA（酶联免疫吸附试验）检测血液 GCD 59的水平，现在正在开发一种新的测试方法，以测量尿液中GCD 59的水平。 床旁（POC）格式。POC尿检GCD 59有可能彻底改变糖尿病领域 因为它将为医生和患者提供一个简单、准确、与病因相关且易于使用的 诊断测试1）有效筛查和诊断糖尿病，糖尿病前期和GDM，2）监测治疗 有效性和3）评估发展这些破坏性和危及生命的并发症的风险 条件该SBIR直接进入第二阶段提案详细说明了开发一种可靠的尿液POC检测方法的计划 GCD 59。该项目建立在学术原型生成的大量概念验证数据的基础上 哈佛大学开发的血浆检测和由美国国家标准化委员会开发的第一代手动GCD 59检测。 这些共同证明了产品概念的可行性。两种专利抗体 已开发用于提供尿GCD 59/总CD 59比率的定量估计。这些宝贵 试剂已被用于初步研究，以评估的可行性和潜在的临床效用， 尿GCD 59测试，Mellitus在此申请中建议开发。梅里特拉了一个顶级的- 一个在GCD 59、糖化生物学和即时检测开发方面具有专业知识的团队， 这是一种易于使用、准确可靠的POC测试，用于测量尿液中的GCD 59水平。该计划吸引了 从业人员以及国家和国际潜在战略伙伴的利益。作的裁决 SBIR第二阶段拨款将加速尿液GCD 59测试的开发，该测试可能成为 糖尿病筛查、诊断和监测的新标准，造福全世界人民。

Project Abstract Diabetes and pre-diabetes are a high public health priority worldwide because they represent a major cause of morbidity and mortality in the adult population, and both are growing at an epidemic rate around the globe. Diabetes and pre-diabetes currently affect close to 9% of the world population and it is estimated that the global prevalence will increase almost 50% over the next 20 years. Mellitus, LLC is developing a novel test for screening, diagnosis and monitoring individuals with diabetes, pre-diabetes and gestational diabetes (GDM). The test is based on the novel biomarker glycated CD59 (GCD59), which was licensed exclusively by Mellitus from Harvard University. Important features of the biomarker are that it 1) is pathogenically relevant because of its mechanistic link to the development of diabetic complications, 2) is present not only in blood but also in urine and other bodily fluids, and 3) has a turn-over rate of ~2 weeks, which is much faster than HbA1c. Mellitus has already developed an ELISA (Enzyme Linked Immunosorbent Assay) test for blood levels of GCD59 and is now in the process of developing a new test to measure urine levels of GCD59 in a point-of-care (POC) format. A POC urine test for GCD59 has the potential to revolutionize the field of diabetes because it will provide physician and patients a simple, accurate, pathogenically relevant and easy to use diagnostic test to 1) efficiently screen and diagnose diabetes, pre-diabetes and GDM, 2) monitor treatment effectiveness and 3) assess the risk of developing the devastating and life-threatening complications of these conditions. This SBIR Direct to Phase II proposal details the plan to develop a robust POC test for urine GCD59. The project builds on extensive proof-of-concept data generated with the academic prototype plasma assay developed at Harvard University and the first-generation manual GCD59 test developed by Mellitus, which together demonstrate feasibility for the product concept. Two proprietary antibodies have been developed to provide a quantitative estimate of the urine GCD59/total CD59 ratio. These valuable reagents have been used in preliminary studies to assess the feasibility and potential clinical utility of the urine GCD59 test that Mellitus proposes to develop in this application. Mellitus has brought together a top- tier team with expertise in GCD59, glycation biology and point-of-care assay development to develop a novel, easy-to-use, accurate and reliable POC test to measure GCD59 levels in urine. This program has attracted the interest of practitioners as well as national and international potential strategic partners. Award of an SBIR Phase II grant would accelerate development of a urine GCD59 test that could potentially become the new standard for screening, diagnosing and monitoring diabetes for the benefit of populations worldwide.