Evaluation and validation of a breath ammonia measurement technology for the improved management of patients with urea cycle defects

SIGNIFICANTLY REDUCED QUALITY AND QUANTITY OF LIFE The Problem Urea Cycle Defects (UCD) Rare inherited disorders Predominantly affect children 600 in UK, 250,000 globally Toxic build up of ammonia Cognitive impairment and neurological damage Lifelong chronic and acute management Constant threat of increased disability and death CPS1 Carbamoyl phosphate synthase 1 deficiency OTC Ornithine transcarbamylase deficiency ASS Argininosuccinate acid synthetase deficiency ASL Argininosuccinate acid lyase deficiency ARG Arginase deficiency NAGS N-acetylglutamate synthase deficiency SIGNIFICANTLY REDUCED QUALITY AND QUANTITY OF LIFE

The Need Difficult to identify elevated ammonia No easy way to measure ammonia Poor acute management Requires high index of suspicion Results in regular hospitalisation Poor chronic management Quality of life Stress Cost of care Risk ACCURATE, CONVENIENT SELF-MANAGEMENT OF AMMONIA LEVELS

Engaging with patients and carers “I cannot deal with upset. I am all over the place and I can feel my ammonia go up and cannot control it. If I had a way of measuring it, I would know when it was critical.” “I go to school, I socialise I have a great life. If I could manage my ammonia, I would be able to avoid catastrophe whilst trying to continue as normal.” “When we have to go to hospital it takes us an hour to get there. It then takes them one hour to assess the situation. Even though we know speed is critical and there should be no delay, we cannot prove to them that something needs to happen. Thus, the ammonia continues rising and rising.”

The Gap Point of care blood ammonia Qualitative breath assays Instrumental breath methods Ammonia breath sensors NOT SUITABLE FOR THE QUANTITATIVE MEASUREMENT OF AMMONIA AT POC

The Ammonia Breath Monitor The solution AmBeR® The Ammonia Breath Monitor Printed conducting polymer nanoparticle sensor technology 10 years of research £900,000 investment 15 high-impact peer reviewed publications 2 patents and 1 trademark Evaluated in normal and patient populations Comparable analytical performance to instrumental methods Low cost, disposable sensors Small portable instrument 40 – 3,000 ppbv, r2 >0.99, rsd <11%

The Questions Can the AmBeR system be used to improve the management of patients with UCDs? Can it be used for the effective measurement of ammonia in the breath of UCD patients? Can it be used to estimate blood ammonia accurately and reliably across the clinical range? Can it be used for home self testing? Will it facilitate remote management? Will it reduce costs? Will it improve quality of life?

The Team Project Leader Dr. Suresh Vijay Dr. Lara Abulhoul Prof. Tony Killard Dr. Lara Abulhoul Prof. Julian Hamilton-Shield Dr. Jo White Dr. Michael Champion

The Plan 2016 2017 2018 2019 Project start Ethics submission Availability of AmBeR system prototypes Prototype prep. Regulatory prep. Lab Verify ability to estimate blood ammonia from breath Clinic Potential of AmBeR UCD for remote management Home Estimations of NHS costs and quality of life Exploitation phase

The AmBeR clinical system Instrument Laptop Sensor cartridge Software Sampling system

The AmBeR R&D clinical system

The sensor How does it work? Plastic cartridge for holding, inserting and removing from instrument Protects sensor layer from damage Green sensor ink which detects ammonia – don’t touch! Silver conductive connectors to connect sensor layer to the instrument

How does it work? Software

AmBeR can measure ammonia in breath What now? AmBeR can measure ammonia in breath We think this can be used as an easier way of measuring ammonia levels in the body However, no-one has yet demonstrated this

What now? Firstly, we want to find out if the levels of ammonia in blood relate to those in breath We then want to see if the levels of ammonia we measure relate to patient health status

If measuring breath ammonia can be used to help manage ammonia levels… What then? If measuring breath ammonia can be used to help manage ammonia levels… We want to develop an AmBeR system that patients and families can use in their own home Simple to use and does not require a separate computer

AmBeR UCD (home use) system Touch screen user interface Insertion of sensor cartridge Flip top operational access Games console style design

Current prototype

Current prototype