We propose to develop a non-invasive device to enable children with urea cycle disorders (and their parents, guardians, and physicians) to actively manage the disorder at home and improve outcomes in the clinic. Urea cycle disorders (UCD) are inborn errors of metabolism that impair one's ability to convert ammonia (NH3), a neurotoxin, into urea, which is renally cleared from the body. An accumulation of ammonia in the body, known as hyperammonemia (HA), initially presents with non-specific behavioral symptoms (e.g., lethargy, hyperactivity), and if not treated can result in seizure, coma, permanent brain damage, and death. Currently, if HA is suspected in a UCD patient, the patient is taken to an emergency department and ammonia concentration is measured in the blood, which is notoriously inaccurate due to the continued production of NH3 in blood samples prior to analysis. This often erroneous measure of blood ammonia dictates the clinical course of treatment for HA, which ranges from administering intravenous fluids, nitrogen scavenging drugs, or in severe cases, dialysis. Children with UCD (and their parents or guardians) currently have no means to manage UCDs at home, and tools available in the clinic are inaccurate and slow, which can result in inadequate or mistreatment of HA. Thus, a significant opportunity exists to improve the health and care of children with UCDs by providing a more effective instrument to monitor NH3 in the body. Our vision is to provide UCD patients and clinicians who care for UCD patients with an accurate, portable, and non-invasive device to monitor a patient's ammonia level by measuring breath-borne ammonia using laser absorption spectroscopy. The envisaged product intends to provide a new means to detect the onset of HA for children at home, enabling treatment to be administered at home before ammonia accumulates to dangerous levels. The product will also enable rapid, real-time, and non-invasive measurement of ammonia, enabling physicians to administer optimal, rate-based treatment of HA in the clinic. In this Phase I Small Business Technology Transfer grant, Lumina Diagnostics proposes to establish the commercial feasibility of such a product by: (1) demonstrating and evaluating two different spectroscopic strategies for measuring gas-phase ammonia to optimize the proposed device in terms of cost and reliability; (2) demonstrating a novel breath sampling technique to increase signal levels and simplify breath collection procedures for children; (3) conducting a pilot clinical study using the proposed sensor to measure the relationship between blood-ammonia and breath- borne ammonia in UCD patients and cases of hyperammonemia. Accomplishment of these objectives will remove the main technological and clinical risks related to the proposed product. Successful commercialization of the product by Lumina Diagnostics will allow children with UCD (and their parents and guardians) to restore some normalcy to their lives by being able to actively manage their disease.
Public Health Relevance Statement: Public Health Relevance: This research evaluates a novel approach to providing a non-invasive diagnostic tool that has the potential to significantly improve clinical diagnosis and at-home-management of hyperammonemia in patients with urea cycle disorders via measurement of ammonia in the breath. Rapid, non-invasive measurements of ammonia will enable optimal, tailored clinical care for hyperammonemic UCD patients, as well as at-home management of UCD via preventative, rate-based treatment for hyperammonemia, which will enable UCD patients (and their families) to live their lives with more normalcy (e.g., by being able to attend school). Thus the proposed research directly advances the NIH mission of applying knowledge to enhance health, lengthen life, and reduce the burdens of illness.
Project Terms: absorption; Accident and Emergency department; Address; Adoption; Adsorption; Ammonia; base; Behavior; Behavioral Symptoms; Biological Markers; Blood; Blood specimen; Brain Injuries; Breath Tests; burden of illness; Businesses; Caring; Cessation of life; Characteristics; Child; Child health care; Clinic; Clinical; clinical care; clinical Diagnosis; Clinical Research; clinical risk; clinically relevant; Collection; Coma; commercialization; cost; Cost-Benefit Analysis; design; Desire for food; Detection; Development; Devices; Diagnostic; Dialysis procedure; Disease; Evaluation; evaporation; Family; Gases; Genetic Predisposition to Disease; Grant; Health; Home environment; Hospitals; human disease; Hyperactive behavior; Hyperammonemia; improved; Inborn Errors of Metabolism; infrared spectroscopy; instrument; Investigation; IV Fluid; Knowledge; Laboratories; Lasers; Laws; Lead; Life; Literature; maltreatment; Measurement; Measures; Methods; Mission; Monitor; monitoring device; Motivation; neonate; Nervous System Trauma; Neurotoxins; Nitrogen; Normalcy; novel; novel strategies; Outcome; Parents; Patient Monitoring; Patients; Pediatric Hospitals; Pharmaceutical Preparations; Phase; Physicians; Procedures; Production; Protocols documentation; prototype; public health relevance; quantum; Reaction Time; Research; Sampling; Schools; Seizures; sensor; signal processing; Signal Transduction; Solubility; Spectrum Analysis; Surface; Techniques; Technology Assessment; Technology Transfer; Thermodynamics; Time; tool; United States National Institutes of Health; Universities; Urea; urea cycle; Validation; vapor; Vision; Water; water solubility; Work
