- Exogenous Volatile Organic Compound (EVOC®) Probes represent an important advance to support the implementation of Breath Biopsy in a wide range of applications
- Paper published in peer-reviewed Journal of Breath Research describes the use of EVOCs as metabolic pathway-specific probes
- Initial focus on research into drug metabolism, liver function, and Nonalcoholic Fatty Liver Disease (NAFLD) and Nonalcoholic Steatohepatitis (NASH)
Cambridge, UK, 18 June 2019: Owlstone Medical, the global leader in Breath Biopsy® for applications in early disease detection and precision medicine, today announces the development of an innovative alternative approach to breath-based testing through the utilization of Exogenous Volatile Organic Compound (EVOC®) Probes. The novel probes will enable Breath Biopsy to be deployed for a wider range of applications.
Recently published in the Journal of Breath Research, the potential of EVOC Probes to explore metabolic pathways is described, along with the potential of Owlstone Medical’s Breath Biopsy EVOC Probes Research Kit to help transition breath testing from the lab into the clinic (https://doi.org/10.1088/1752-7163/ab1789).
Exhaled human breath contains over 1,000 volatile organic compounds (VOCs). These chemicals can originate from within the body (endogenous) but also can come from external sources such as diet, prescription drugs and environmental exposures (exogenous). To date, VOC-based breath research has focused on the identification of endogenous VOCs as disease biomarkers, however few tests based on this approach have made it to the clinic.
There are multiple reasons this is the case, which Owlstone Medical is directly addressing through its innovative Breath Biopsy platform and through large and robust clinical trials run on behalf of clients or its own studies to identify and validate endogenous biomarkers. Now, to broaden the range of tools available to address high need areas and to accelerate the launch of commercial tests, the company has pioneered the use of EVOC Probes to investigate the onset, progression, and treatment of disease.
The concept of administering exogenous probes to assess metabolic function in the body on breath has been applied previously but has been limited to stable isotope-labelled probes. Owlstone Medical’s novel approach is to develop and deploy a range of externally administered compounds that fall under the FDA GRAS (Generally Recognized As Safe) list and through breath analysis, explore how they are absorbed, metabolized or excreted to give a direct measure of metabolic activity and organ function.
The compounds that will be incorporated into EVOC Probes operate through known metabolic pathways and so measurement of their breakdown provides direct insight into the functioning of that pathway. Further, as these compounds are not normally present on breath, their detection and measurement provide a very clear signal that offers the potential for a new wave of substrate-based breath tests.
Three early areas of focus for Owlstone Medical in the application of EVOC Probes are drug metabolism, liver function, and Nonalcoholic Fatty Liver Disease (NAFLD) and Nonalcoholic Steatohepatitis (NASH).
Billy Boyle, co-founder and CEO at Owlstone Medical, said: “EVOC Probes represent a powerful new approach to breath-based diagnosis. By deploying this complementary technology alongside endogenous VOC biomarker discovery efforts as part of our Breath Biopsy platform, Owlstone Medical is now able to bring a much broader range of tools to bear in solving the challenge of the earlier detection of disease and the more efficient and effective discovery, development, and use of novel therapeutics.”
Notes to Editors:
For more information please contact:
Sarah Jeffery, Zyme Communications
+44 (0)7771 730919
What is Breath Biopsy®?
Breath Biopsy represents an entirely new way to measure the chemical makeup of breath by measuring volatile organic compounds (VOCs), gaseous molecules that can be sampled quickly and non-invasively from breath and enabling whole-body sampling. These compounds are produced as the end product of metabolic processes within the body, meaning that underlying changes in metabolic activity can produce particular patterns of VOCs characteristic of specific diseases.
VOCs originating from all parts of the body are captured in breath, making Breath Biopsy applicable to a wide range of diseases including cancer, inflammatory disease, infectious disease, metabolic disease, cardiovascular disease and respiratory disease. The nature of Breath Biopsy, and VOC biomarkers, make them perfectly suited to addressing two of the major challenges of healthcare today: early detection and precision medicine.
Breath collection is carried out using Owlstone Medical’s ReCIVA® Breath Sampler, which ensures reliable, reproducible collection of VOCs. Subjects breathe a controlled supply of air, and samples of their exhaled breath are captured and stabilized on Breath Biopsy Cartridges, which can then be shipped for analysis with Owlstone Medical’s Breath Biopsy analytical platform, using mass spectrometry or FAIMS to determine their VOC profile. Advanced data analytic techniques can then be applied in order to pinpoint the VOCs of interest.
About Exogenous VOC (EVOC) Probes
Exogenous compounds are continuously introduced into the body through diet, medications, environment and lifestyle choices, resulting in many cases of those compounds or the products of their metabolism being detectable on breath. Taking this concept one step further, an exogenous compound can be given to a patient, similar to how fructose is currently applied in the clinic as metabolic probe to assess malabsorption through the gastrointestinal tract. A specific example of how Owlstone Medical is using this approach in EVOC Probes is limonene, a compound that falls under the FDA GRAS (Generally Recognized As Safe) list and is metabolized in the body by the cytochrome P450 enzyme 2C9. 2C9 also metabolizes a wide range of drugs including Crestor®, and so by measuring metabolism of limonene on breath, important insights can be gained on how medications like Crestor are likely to be metabolized in an individual.
Early Potential Applications of EVOC Probes:
Approximately 40% of drugs do not work as expected when prescribed. This is largely due to drug metabolism, the biologic processing of drugs from prodrugs into their active forms, and the breaking down of drugs for excretion. When this process goes wrong, a drug can build up in the body to toxic levels or the active form never reach sufficient levels to have the desired therapeutic effect. Knowledge of a patient’s drug metabolism status therefore allows clinicians to make more informed decisions as to which drugs to prescribe and at what dose.
Owlstone Medical is exploring the development of a test that uses EVOC probes that are metabolized by the same P450 enzymes that process medications, and so by measuring their levels on breath and their rate of processing and breakdown, a reliable phenotypic profile that is more predictive than genotype alone can be built.
For a range of conditions, it is critical for clinicians be able to reliably measure liver function to detect and monitor the progression of disease or the impact of therapy. A range of diagnostic tests currently exist, however they produce results that can originate from a range of physiological inputs and so are used in concert with clinical presentation to suggest further investigations. In contrast, a Breath Biopsy assay from Owlstone Medical utilizing EVOC Probes has the potential to generate a clear and unambiguous measurement of liver function and potentially to distinguish among different types of liver disorders by measuring the activity of key liver enzymes.
Nonalcoholic Fatty Liver Disease (NAFLD) and Nonalcoholic Steatohepatitis (NASH)
NAFLD is a condition in which excess fat is stored in the liver but with alcohol abuse not being the underlying cause. In approximately 25% of cases, NAFLD develops into NASH where inflammation and liver cell damage can cause fibrosis, or scarring, of the liver, and can lead to cirrhosis or liver cancer.
Gold standard testing for the diagnosis of these diseases involves a range of expensive and time-consuming tests followed by liver biopsy for confirmation. EVOC Probes offer a promising alternative which is being explored to determine whether breath analysis can be deployed as a novel non-invasive approach to monitor NAFLD and NASH disease progression.