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.

项目概要/摘要 该项目建议开发技术以提供苯丙氨酸 (Phe) 的低成本监测 通过简单、无创的家庭尿液检测来检测血液中的水平，以便能够通过以下方式进行日常监测： 苯丙酮尿症 (PKU) 患者。 PKU 也称为苯丙氨酸羟化酶缺乏症，是一种罕见的疾病 先天性代谢缺陷，在美国发生的频率约为 15,000 名儿童中就有 1 名。如果不治疗，Phe 血液中的水平上升至神经毒性水平，导致神经损伤和智力障碍 出生后几个月内。通过新生儿筛查发现后，治疗包括终身严格 使用低 Phe 饮食和药物控制代谢，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。干血斑样本允许 监测 Phe 水平，建议在生命的前五年每周一次，此后每月一次。 然而，Phe 血液检测通常需要 5 至 10 天才能返回实验室结果，因此增加了 对血液 Phe 水平中未被识别的峰值的敏感性。国家认识到这一现状， 北京大学联盟已将开发用于日常 Phe 监测的家庭测试作为最重要的技术之一 北京大学社区的迫切需求。就像家用血糖仪帮助糖尿病患者一样 为了对他们的状况进行日常监测和控制，北京大学的家用仪表将能够实现关键的 以改善健康和长期结果所需的精度控制 Phe 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，可以提高光学灵敏度 使用简单的比色法读出尿液中特定 Phe 代谢物的水平。这个提议 项目将扩展这些成就，生产出完整、简单、廉价的家庭尿液检测 称为 Rally Phenometer 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。具有优化颜色敏感性的吸收优惠券将集成在一个完整的系统中 一次性测试，可以浸入尿液样本中并插入低成本的仪表设备中。这米 将由 Circa Bioscience 开发，用于获取尿液检测优惠券的图像，执行必要的操作 比色法测量，并向用户或护理人员报告估计的血液 Phe 水平。分析型 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， 南卡罗来纳州针对 PKU 患者的主要临床机构，旨在证明两者之间的相关性 尿液和血液中 Phe 水平的代谢水平，并验证 Rally Phe 的临床基础 诺米特。除了PKU之外，我们创新的优惠券设计，结合提高的敏感度 比色读数，将使家庭尿液测试的发展成为可能，用于监测各种 条件，包括其他先天性代谢缺陷和肾脏疾病。