Phenylketonuria (PKU) is a serious inborn metabolic disorder affecting 1 out of every 15,000 children born in the U.S. annually. Characteristic effect of PKU is the impaired capability of the body to convert the amino acid phenylalanine (Phe) to tyrosine and, as a result, Phe level is elevated in the blood stream. While Phe is required for normal growth and brain development, excess Phe leads brain damage and ultimately severe intellectual impairment. The effects of prolonged exposure to Phe is much more pronounced during childhood and pregnancy, resulting in growth retardation and neurological impairment in children, development delay, microcephaly and congenital heart disease in fetuses. Therefore, patients with PKU need carefully control and monitoring of their blood Phe level for their whole lives, especially for infants, children and pregnant women. To control blood Phe levels, a specially designed low Phe diet, which is devoid of protein-containing food, must be followed. Since Phe diet are difficult to follow and prolonged exposure to elevated Phe as well as frequent fluctuation of blood Phe impacts normal growth and brain development, blood Phe levels are routinely monitored for patients with PKU. However, monitoring blood Phe today requires long turn-around time, since blood sample needs to be first collected via a blood drawn or on filter card, then analyzed in a clinical laboratory using costly and sophisticated instrument. Hence, many PKU patients can only maintain a suboptimal blood Phe levels, even they are willing to make dietary adjustment. Therefore, home Phe monitoring providing with immediate test result is imperative to achieve better health outcomes and to avoid neurocognitive issues. Although methods have been reported for monitoring Phe at home, most of them rely on optical detection that is vulnerable to interferences from colored species in clinical samples, or electrochemical detection that uses sophisticated assay methods or highly modified electrochemical detectors, limiting their commercial potentials. Based on this compelling need and our recent discovery that many commercially available Blood Glucose Meters (BGMs) can measure levels of NADH, a cofactor in many enzymatic assays, we propose to repurpose the BGM widely used by diabetics for PKU patients to monitor blood Phe levels. We have developed a technology that allows the direct use of existing glucose test strips for quantification of Phe, via an enzyme phenylalanine dehydrogenase that generates NADH in the presence of Phe. Furthermore, we have developed a customized meter to improve the NADH sensitivity while still using existing glucose test strips. In this Phase I project, we will focus on demonstrating the feasibility by developing a BGM based Phe assay followed by sensor strip development. By leveraging todays BGM platform, we can drastically reduce the time and cost associated with medical device R&D and scale up production, while delivering an easy-to-use and affordable solution for PKU patients to monitor their Phe levels rapidly at home or at any point of care setting.
Public Health Relevance Statement: Project Narrative This SBIR Phase I proposal aims to take advantage of existing glucose meter technology by employing an innovative approach to develop a home-use device for measuring blood levels of phenylalanine, which is routinely monitored to ensure patients with phenylketonuria, or PKU, have properly maintained their blood phenylalanine level. Providing PKU patients with an affordable, easy-to-use and rapid monitoring device can significant improve the efficiency and efficacy in managing their symptoms, leading to a healthier and more productive life.
Project Terms: abstracting; Address; Adult; Affect; Age; Amino Acids; assay development; Ataxia; base; Biological Assay; Blood; Blood - brain barrier anatomy; Blood Glucose; Blood Glucose Self-Monitoring; Blood specimen; Brain; Brain Injuries; Characteristics; Child; Child Development; Childhood; Classical phenylketonuria; Clinic; Clinical; cofactor; Color; commercialization; congenital heart disorder; cost; Data; design; Detection; detector; Development; Developmental Delay Disorders; Devices; Diabetes Mellitus; diabetic; Diagnosis; Diet; Effectiveness; Electrodes; Ensure; Enzymes; Exposure to; Family; Feedback; Fetus; Food; Foundations; Glucose; glucose monitor; Growth; Health; Home environment; Human; Impairment; improved; Infant; innovation; instrument; Laboratories; Life; Marketing; Measures; Medical; Medical Device; Metabolic Diseases; meter; Methods; Microcephaly; Monitor; monitoring device; NADH; Neurocognitive; Neurologic; neurotoxic; Newborn Infant; Nutrient; Optics; Outcome; Oxidoreductase; Patient Monitoring; Patients; Performance; Phase; Phenylalanine; Phenylalanine Hydroxylase; Phenylketonurias; Physicians; point of care; Pregnancy; Pregnant Women; Printing; Procedures; Production; Protein-Restricted Diet; Proteins; prototype; Reaction Time; Reagent; Recovery; Reporting; Research; research and development; Risk; Sampling; scale up; Seizures; sensor; Serum; Signal Transduction; Small Business Innovation Research Grant; Stabilizing Agents; Stream; Symptoms; System; Technology; Test Result; Testing; Time; Tyrosine; Validation; Variant; Visit; Work
