Breath ammonia monitoring device for children with urea cycle disorders

DESCRIPTION provided by applicant 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 oneandapos s ability to convert ammonia NH 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 NH 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 NH 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 patientandapos 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 demonstrating and evaluating two different spectroscopic strategies for measuring gas phase ammonia to optimize the proposed device in terms of cost and reliability demonstrating a novel breath sampling technique to increase signal levels and simplify breath collection procedures for children 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 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