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

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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.