ADA2 Diagnostic Platform: Point-of-care test for determination of patient enzyme levels for diagnosis of the rare disease Deaminase2 Deficiency (DADA2)

摘要 本申请是关于国家推进转化科学中心 SBIR/STTR综合征求（研究优先事项：解决 罕见疾病的快速诊断和/或临床管理）。体外诊断解决方案有限责任公司 （IVDS）建议开发一种即时（POC）血液测试，以快速确定患者酶 水平用于诊断罕见疾病，腺苷脱氨酶2（DADA 2）缺乏症。 DADA 2是一种单基因隐性遗传疾病，导致翻译减少或不正确 ADA 2酶。ADA 2在血清中的全部生理作用尚未完全阐明， 但已证实，ADA 2缺陷导致严重至致命的疾病， 表型包括系统性血管炎、儿科和早发性中风、骨髓衰竭， 和免疫缺陷。此外，由于对这种酶的兴趣增加，异常ADA 2 活性已被研究并建议作为几种感染性疾病的部分驱动因素或生物标志物。 和慢性疾病。目前，ADA 2活性的测定是在开始时开始的。 症状，并需要昂贵和耗时的实验室分析，提出了一个 给患者和护理人员带来沉重负担。快速准确的POC测试将具有 对DADA 2的理解、诊断、管理和治疗产生了深远的影响， 对医疗保健行业产生广泛的治疗和经济影响。IVDS开创了一种 通用POC测试平台，基于经济高效、便携且易于使用的设备， 通过手指针刺、脚跟针刺或 微量容器抽取。该平台基于通过反射计进行的比色检测 嵌入LED面板，覆盖目前使用的85%以上的比色指示器。 市场测试条由1）样本铺展层，2）初级血液分离层， 膜，3）次级血液分离膜，和4）可定制的试剂层，其 可以被调节以提供用于检测其它分析物的“即插即用”机会。目前 该平台正在我们的PKU Now、Bili Now、Hgb Now、IVDS Liver Panel和 PreQuine平台（G6 PD缺陷测定）。IVDS直接与研究合作 机构和非营利基金会开发有前途的技术，改善健康和 拯救生命，具有强大的商业化潜力-因此与目的非常一致 这个融资机会。除了彻底改变DADA 2的管理， 这笔资金将使IVDS能够支持IVDS POC平台的商业化， 对罕见病管理和医疗保健行业产生重大影响。

Abstract This application is in regard to the National Center for Advancing Translational Sciences SBIR/STTR Omnibus Solicitation (Research Priority: Tools and technologies that address the rapid diagnosis and/or clinical management of rare diseases). In Vitro Diagnostic Solutions, LLC (IVDS) proposes to develop a point-of-care (POC) blood test to rapidly determine patient enzyme levels for the diagnosis of the rare disease, deficiency of adenosine deaminase 2 (DADA2). DADA2 is a monogenic, recessive genetic condition that leads to reduced or improper translation of the ADA2 enzyme. The full physiological role of ADA2 in serum has yet to be fully elucidated, but it is confirmed that deficiencies in ADA2 result in a severe to fatal condition with highly variable phenotypes including systemic vasculitis, pediatric and early-onset stroke, bone marrow failure, and immunodeficiency. Furthermore, due to increased interest in this enzyme, abnormal ADA2 activity has been investigated and suggested as a partial driver or biomarker for several infectious and chronic diseases. Currently, determinations of ADA2 activity are initiated upon the onset of symptoms and require expensive and time-consuming laboratory analysis, presenting a significant burden on patients and care takers. A rapid and accurate POC test would have a profound impact on the understanding, diagnosis, management, and treatment of DADA2 with broad therapeutic and economic impacts on the healthcare industry. IVDS has pioneered a universal POC testing platform based on a cost-effective, portable, and simple-to-use device for determining accurate concentrations of analytes in whole blood from a finger-stick, heel-stick, or microtainer draw. The platform is based on colorimetric detection via a reflectance meter embedded with a panel of LEDs chosen to cover over 85% of colorimetric indicators currently on the market. Test strips consist of 1) a sample spreading layer, 2) a primary blood separation membrane, 3) a secondary blood separation membrane, and 4) a customizable reagent layer that can be modulated to provide “plug-and-play” opportunities for detecting other analytes. Currently this platform is being implemented in our PKU Now, Bili Now, Hgb Now, the IVDS Liver Panel and the PreQuine Platform (G6PD deficiency determination). IVDS cooperates directly with research institutions and non-profit foundations to develop promising technologies that improve health and save lives, with a strong potential for commercialization - thus aligning excellently with the purpose of this funding opportunity. Beyond revolutionizing the management of DADA2, securing this funding will allow IVDS to support the commercialization of the IVDS POC platform which will have a substantial impact on rare disease management and the healthcare industry.