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

开发用于在家监测 PKU 血液 Phe 水平的尿液检测

• 批准号: 10822515
• 负责人: Kevin D Champaigne
• 金额: $ 29.57万
• 依托单位: CIRCA BIOSCIENCE, LLC
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-09-20 至 2024-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10822515
• 关键词: Achievement; Acids; Affect; Amino Acids; Biological Sciences; Birth; Blood; Blood Tests; Blood specimen; Caregivers; Caring; Child; Classical phenylketonuria; Clinical; Clinical Research; Clinical Trials; Code; Color; Colorimetry; Communities; Compensation; Computer software; Data; Detection; Development; Devices; Diabetes Mellitus; Diagnostic; Diagnostic tests; Diet; Dryness; Enzymes; Family; Female; Foundations; Frequencies; Genetic; Goals; Health; Home; Image; Image Analysis; Impaired cognition; Inborn Errors of Metabolism; Individual; Institutional Review Boards; Intellectual functioning disability; Intuition; Kidney Diseases; Laboratories; Legal patent; Life; Lighting; Liver; Manuals; Measurement; Measures; Medical Device; Metabolic Control; Methods; Mission; Monitor; Mutation; Nature; Neonatal Screening; Nervous System Trauma; Neurologic Effect; Optics; Outcome; Patients; Performance; Periodicals; Pharmaceutical Preparations; Phase; Phenylalanine; Phenylalanine Hydroxylase; Phenylketonurias; Predisposition; Preparation; Procedures; Process; Recommendation; Regulation; Reporting; Research; Research Personnel; Research Project Grants; Sales; Sampling; Series; Small Business Technology Transfer Research; South Carolina; Spottings; Stream; System; Systems Analysis; Techniques; Technology; Test Result; Testing; Time; Tyrosine; United States National Institutes of Health; Universities; Urine; commercial application; commercialization; comorbidity; cost; design; diabetic; diagnostic technologies; dietary; glucose monitor; healthy lifestyle; home test; improved; innovation; male; manufacture; member; meter; neurotoxic; new technology; non-invasive system; novel; pharmacologic; phase 1 study; prototype; rare genetic disorder; response; screening; software systems; standard measure; success; targeted treatment; technological innovation; technology development; user-friendly

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.

项目总结/摘要 本项目提出开发低成本监测苯丙氨酸（Phe）的技术 血液中的水平通过一个简单的，非侵入性的，在家里尿检，以便能够每天监测， 苯丙酮尿症（PKU）苯丙氨酸羟化酶缺乏症也被称为苯丙氨酸羟化酶缺乏症， 先天性代谢缺陷，在美国发生的频率约为1/15，000儿童。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 在出生后的几个月内。通过新生儿筛查检测后，治疗涉及终身严格的 使用低Phe饮食和药物进行代谢控制，以将血液Phe水平维持在健康范围内。如果 如果控制得当，正常的健康和发育是可以预期的。干血斑样本 监测Phe水平，建议在生命的前五年每周监测一次，此后每月监测一次。 然而，Phe的血液测试通常需要5至10天才能返回实验室结果，因此增加了 对血液中苯丙氨酸水平未识别峰值的敏感性。鉴于目前的问题，国家 北京大学联盟已经确定，开发一种用于日常Phe监测的家庭测试是最重要的测试之一。 北京大学社区的迫切需要。就像家用血糖仪让糖尿病患者 参与日常监测和控制他们的状况，北大的家庭仪表将使关键的 以改善健康和长期结果所需的精确度控制Phe水平。的市民 克莱姆森大学的一个研究小组最近获得了一项专利技术，该技术能够提高光学传感器的灵敏度。 使用简单的比色法读出尿中特定Phe代谢物的水平。这一拟议 一个项目将在这些成就的基础上进行扩展，以生产一种完整、简单、廉价的家庭尿检 一个名为Rally Phe-nometer的系统，使PKU患者能够每天监测他们的血液Phe水平 以非侵入性的方式。具有优化颜色灵敏度的吸收剂试样将集成在完整的 一次性测试，可以浸入尿样，并插入到低成本的仪表设备。这个仪表 将由Circa Bioscience开发，以获取尿液测试试样的图像，执行必要的 比色法测量，并将估计的血液Phe水平报告给用户或护理人员。分析 该系统的性能将在目标1中得到验证。我们还将与格林伍德遗传中心合作， 南卡罗来纳州的PKU患者的主要临床设施，以证明 代谢物水平存在于尿液和血液Phe水平，并验证拉力赛Phe的临床基础， 纳米。除了PKU，我们创新的优惠券设计，结合增加的灵敏度， 比色读数，将使发展在家里尿检监测各种各样的 条件，包括其他先天性代谢缺陷和肾脏疾病。