权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

A rapid and portable test for home monitoring of phenylalanine levels by patients with phenylketonuria using a blood glucose meter

使用血糖仪在家监测苯丙酮尿症患者苯丙氨酸水平的快速便携式测试

基本信息

批准号：
9346910
负责人：
Tian Lan
金额：
$ 22.35万
依托单位：
GLUCOSENTIENT, INC.
依托单位国家：
美国
项目类别：
财政年份：
2017
资助国家：
美国
起止时间：
2017-04-01 至 2019-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9346910
关键词：
Address Adult Affect Age Amino Acids Ataxia 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 Color Custom Data Detection Development Developmental Delay Disorders Devices Diabetes Mellitus Diagnosis Diet Effectiveness Electrodes Ensure Enzymes Exposure to Family Feedback Fetus Food Foundations Glucose Growth Health Home environment Human Impairment Infant Laboratories Life Measures Medical Medical Device Metabolic Diseases Methods Microcephaly Monitor NADH Neurocognitive Neurologic Newborn Infant Nutrient Optics Outcome Oxidoreductase Patient Monitoring Patients Performance Phase Phenylalanine Phenylalanine Hydroxylase Phenylketonurias Physicians Pregnancy Pregnant Women Procedures Production Protein-Restricted Diet Proteins Reaction Time Reagent Recovery Reporting Research Risk Sampling Seizures Serum Signal Transduction Small Business Innovation Research Grant Stabilizing Agents Stream Symptoms System Technology Test Result Testing Time Tyrosine Validation Variant Visit Work assay development base cofactor commercialization congenital heart disorder cost design detector diabetic glucose monitor improved innovation instrument meter monitoring device neurotoxic point of care portability prototype research and development scale up sensor

项目摘要

Project Summary/Abstract 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 today’s 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.

项目总结/文摘