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重视的公共卫生问题，因为它们是一个主要原因 在成年人口中，发病率和死亡率都在上升，而且这两者在全球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着世界上近9%的人口，据估计， 在接下来的20年里，全球流行率将增加近50%。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)。这项测试是基于独家授权的新型生物标志物糖化CD59(GCD59) 由哈佛大学的梅特莱斯主持。生物标志物的重要特征是它1)是致病的 因为它与糖尿病并发症的发展有关，2)不仅存在 在血液中，也在尿液和其他体液中，以及3)有~2周的周转率，这要快得多 而不是糖化血红蛋白。糖尿病公司已经开发出一种用于血液的酶联免疫吸附试验 GCD59的水平，目前正在开发一种新的测试方法来测量尿中GCD59的水平 护理点(POC)格式。GCD59的POC尿液检测有可能给糖尿病领域带来革命性的变化 因为它将为医生和患者提供一个简单、准确、与病原学相关的、易于使用的 诊断性测试用于1)有效地筛查和诊断糖尿病、糖尿病前期和妊娠期糖尿病，2)监测治疗 有效性和3)评估发生破坏性和危及生命的并发症的风险 条件。这份SBIR直接到第二阶段的提案详细说明了开发一种可靠的尿液POC测试的计划 GCD59。该项目建立在用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测定法和由 这两个因素共同证明了产品概念的可行性。有两种专有抗体 用于提供尿GCD59/总CD59比率的定量估计。这些贵重物品 试剂已被用于初步研究，以评估该技术的可行性和潜在的临床应用价值。 糖尿病公司建议在此应用中开发的尿液GCD59检测方法。糖尿病带来了一件上衣- Tier团队拥有GCD59、糖基化生物学和护理点检测开发方面的专业知识，以开发一种新的、 使用简单、准确和可靠的POC检测尿液中的GCD59水平。这个节目吸引了 实践者以及国家和国际潜在战略伙伴的利益。授予一名 SBIR第二阶段拨款将加快尿液GCD59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，造福于世界各地的人群。

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.