Simple Breath Test for Ammonia for Monitoring Blood Ammonia Levels for UCD Patients

PROJECT SUMMARY This project proposes the development of technology to provide a quick, low-cost, non-invasive method for monitoring the concentration of ammonia in the bloodstream for individuals with a urea cycle disorder (UCD) by a simple exhaled breath test for ammonia. A UCD is a rare inherited metabolic disorder that is caused by a genetic defect in the urea cycle that occurs in the liver that normally converts ammonia that is generated by protein metabolism into urea, which is then cleared by the kidneys. If untreated, a UCD can cause the buildup of ammonia in the blood stream to life-threatening neurotoxic levels. Persons with a UCD strive to maintain their blood ammonia levels within a normal range by a low-protein diet and medications. Despite these efforts, conditions such as illness, stress, trauma, or simply change in diet can result in elevated ammonia levels (hyperammonemia) with the need to go to the emergency room to initiate IV treatment along with blood tests to assess ammonia levels. Unfortunately, symptoms of elevated blood ammonia can be non-specific and similar to non-hyperammonemic conditions, such as the flu (e.g., nausea, vomiting, headache, fatigue). However, because of the risk of neurological damage if high ammonia levels are actually occurring, patients are recommended to go to the emergency room for treatment and evaluation whenever likely symptoms occur. This situation leads to unnecessary trips to the emergency room when hyperammonemia is not actually causing the illness and the associated costs. A solution to this problem would be the availability of a point-of- care test method for assessing blood ammonia level that persons with a UCD and/or medical staff could use to determine whether or not a hyperammonemic condition was actually occurring. The specific need for this type of product is highlighted in the 2018 FDA/NIH report entitled “Unmet Medical Device Needs for Patients with Rare Diseases.” At this time, however, no such test method exists. To meet this need, we are developing a simple exhaled breath test for ammonia for assessing blood ammonia level. Preliminary clinical studies conducted with two UCD patients as proof-of-principle of this test have shown high correlation with blood ammonia level and the ability to indicate whether or not a condition of elevated blood ammonia was occurring. The overall objectives of this Phase-I project are to further develop and optimize this test system specifically for the UCD patient community in preparation for subsequent large-scale clinical studies in a follow-up Phase-II program. Specific Aim 1 is to refine the sensitivity range of the ammonia sensor discs specifically for the UCD application and to assess the potential influence of temperature, humidity, and possible interfering substances on their colorimetric response. Specific Aim 2 is to design and produce a dedicated sensor-reading instrument to automate the test system and provide a quantitative digital readout of breath ammonia concentration in parts-per-billion in preparation for large-scale clinical evaluation. This technology also has potential for extension for kidney and liver disease and h. pylori infection applications.