Abstract- Breath test diagnostics offer great promise in rapid, point of care and non-invasive diagnostics, especially for lung infection in diseases such as tuberculosis and cystic fibrosis. The dominant approach in the field is to obtain 'signatures' of a high number of volatile compounds in exhaled breath (the volatome) to differentiate between health and disease and to discriminate between pathogens. In contrast, we have focused upon delivering stable isotope labeled tracers to the lung, where unique microbial biochemistry converts them to labeled volatiles for analysis, generally focusing upon a single microbial enzyme, although some multiplexing is possible. The price we pay for our specificity is the regulatory burden of delivering inhaled compounds. I will discuss our successes and failures from in vitro systems to the clinic, what we have learned from them, and what we see happening in the future. Examples will include enzymes important in microbial pathogenesis and drug resistance, and from BSL 1 to select agents. I will also discuss the possibilities of 'stable isotope editing' to improve the specificity or sensitivity of volatome signature-based techniques. Finally, I will briefly discuss our experiences of using a stable isotope labeled drug to enhance its activity against TB through mass independent effects.
Disclosure- Graham Timmins is also co-founder of Avisa Pharma, developing stable isotope breath tests of lung infection, and is also co-founder and Chief Scientific Officer of SpinCeutica, developing labeled TB drugs for drug resistant-TB.
Biography- Dr Timmins received his degree and PhD in Biochemistry from Leeds UK, and held post-doctoral and research faculty positions at York (Dept. Chemistry with Mike Davies), Dartmouth College (EPR Center with Hal Swartz) and UWCM Cardiff (EPR Imaging with Simon Jackson). He was recruited to the College of Pharmacy, UNM in 2001 where he remains. An initial focus in free radical biology and EPR turned (quite by accident) into a deep interest in the pathogenesis, diagnosis and treatment of lung infections such as TB, with a specialty in using stable isotopes in these studies. Lately, a major focus has been the clinical application and commercialization of many research findings, co-founding a clinical-stage breath test diagnostic company (AvisaPharma) and co-founding an early stage TB drug company (SpinCeutica).