Tapping Into Metabolites To Overcome R&D Challenges And Develop Novel Biomarkers: Part 1

As we continue to strive to mine the genome for clues that can assist in understanding susceptibility to disease, selection of better targets for combating disease, and the biomarkers delineating response, a key source of data that can either lead or strengthen this pursuit is not always part of this equation.

So what is this data and why would one ever exclude it? Metabolites or metabolism is the data and the reason for its occasional exclusion in answering these questions is chiefly because of our devotion to genomics as the source to these answers.

While we should retain our commitment to understanding the genetic basis of these questions, it is important to remind ourselves that metabolites have been and continue to be a staple for clinical and in vivo decision making (fig. 1). Metabolites (cholesterol, glucose, bilirubin, creatinine, thyroid hormone) are used as routine barometers for assessing diabetes, heart disease, renal and hepatic function. In screening newborns for inborn errors of metabolism (IEMs), the levels of blood metabolites are used as surrogates for signifying a clinical condition emanating from a genetic mutation. Importantly, more subtle phenotypes (e.g. susceptibility to a disease, response to a drug, prognosis) also have a chemical fingerprint in biofluid as has been more fully illustrated with recent results with highly sensitive modern technologies¹. Thus there is a strong and well established association between the metabolite and the phenotype.