Development of a Urine Test for At-Home Monitoring of Blood Phe Levels for PKU

项目摘要/摘要 该项目建议开发低成本监测苯丙氨酸(Phe)的技术。 通过一种简单的、非侵入性的家庭尿液测试来检测血液中的水平，以便通过 苯丙酮尿症(PKU)患者。PKU也称为苯丙氨酸羟化酶缺乏症，是一种罕见的 新陈代谢的先天错误，在美国大约每15,000名儿童中就有1名发生。如果不治疗，Phe 血液中的水平上升到神经毒性水平，导致神经损伤和智力残疾 在出生的几个月内。新生儿筛查发现后，治疗涉及终身严格 使用低Phe饮食和药物控制代谢，以将血液Phe水平维持在健康范围内。如果 如果控制得当，健康和发育正常是可以预期的。干血点样本允许 监测苯丙氨酸水平，建议在生命的头五年每周监测一次，此后每月监测一次。 然而，Phe的血液检测通常需要5到10天的时间才能返回实验室结果，因此增加了 对血液中无法识别的苯丙氨酸水平峰值的敏感性。认识到目前的这个问题，国家 北大联盟已经确定，为日常PHE监测开发家庭测试是最重要的测试之一 北大社区的迫切需要。就像家中的血糖仪使糖尿病患者 为了对他们的状况进行日常监测和控制，北大的家用仪表将使关键 以改善健康和长期结果所需的精确度控制苯丙氨酸水平。我们的成员 克莱姆森大学的团队最近获得了专利技术，这些技术能够提高光学元件的灵敏度 用一种简单的比色法读出尿中特定苯丙氨酸代谢物的水平。这项建议 该项目将在这些成果的基础上进行扩展，以生产一种完整、简单、廉价的家庭尿液测试 名为Rally Phe-Nometer的系统，使北大患者能够每天监测他们的血液Phe水平 以非侵入性的方式。颜色敏感度优化的吸收优惠券将集成在一个完整的 一次性测试，可以浸入尿样并插入低成本的计量器中。这个计价器 将由Circa Bioscience开发，以获取尿液测试券的图像，执行必要的 比色法测量，并向使用者或护理人员报告估计的血液Phe水平。分析性 该系统的性能将在AIM 1中得到验证。我们还将与格林伍德遗传中心合作， 南卡罗来纳州为PKU患者设立的初级临床设施，以证明两者之间的相关性 尿液和血液中存在的代谢物水平，并验证Phe-Rally的临床基础。 标记器。除了北大，我们创新的优惠券设计，结合了 比色法读数，将使家庭尿液测试的发展成为可能，用于监测各种各样的 疾病，包括其他先天的新陈代谢错误和肾脏疾病。

PROJECT SUMMARY/ABSTRACT This project proposes the development of technologies to provide low-cost monitoring of phenylalanine (Phe) levels in the blood by a simple, noninvasive, at-home urine test, in order to enable daily monitoring by individuals with phenylketonuria (PKU). Also known as phenylalanine hydroxylase deficiency, PKU is a rare inborn error of metabolism that occurs in the US at a frequency of about 1 in 15,000 children. If untreated, Phe levels in the blood stream rise to neurotoxic levels, leading to neurological damage and intellectual disability within a few months of birth. Following detection by newborn screening, treatment involves lifelong strict metabolic control using a low-Phe diet and medications to maintain blood Phe levels within a healthy range. If properly controlled, normal health and development can be expected. Dried blood spot samples allow monitoring of Phe levels, which are recommended weekly for the first five years of life and monthly thereafter. However, blood tests for Phe typically require 5 to 10 days for lab results to be returned, thus increasing susceptibility to unrecognized spikes in blood Phe levels. In recognition of this present problem, the National PKU Alliance has identified the development of an at-home test for daily Phe monitoring as one of the most pressing needs for the PKU community. In the same way that at-home glucose meters have enabled diabetics to engage in the daily monitoring and control of their condition, an at-home meter for PKU would enable critical control of Phe levels with the precision necessary to improve health and long-term outcomes. Members of our team at Clemson University have recently patented technologies that enable improved sensitivity for the optical readout of levels of a specific Phe metabolite in urine using a simple colorimetric method. This proposed project will expand upon these achievements to produce a complete, simple, inexpensive at-home urine test system, called the Rally Phe-nometer, to enable PKU patients to monitor their blood Phe levels on a daily basis in a noninvasive manner. Absorbent coupons with optimized color-sensitivity will be integrated on a complete disposable test that can be dipped into a urine sample and inserted into a low-cost meter device. This meter will be developed by Circa Bioscience to acquire an image of the urine test coupons, perform the necessary colorimetry measurements, and report the estimated blood Phe level to the user or caregiver. Analytical performance of the system will be validated in Aim 1. We will also partner with the Greenwood Genetic Center, the primary clinical facility in South Carolina for individuals with PKU, to demonstrate the correlation between metabolite levels present in urine and blood Phe levels and to validate the clinical basis for the Rally Phe- nometer. In addition to PKU, our innovative coupon design, combined with the increased sensitivity of the colorimetry readout, will enable the development of at-home urine tests for monitoring a wide variety of conditions, including other inborn errors of metabolism and kidney disease.