FunctionalBiomarkers · Functional Biomarkers as in vitro diagnostic tools for managing patients with chronic disease

The aim of this proposal is to establish a business plan for the development of a new class of Functional Biomarkers as in vitro diagnostic tools for managing patients with chronic disease. The proof of concept will be established by focusing on substrates of the X-prolyl dipeptidylpeptidases (DPP), a family of pleotropic enzymes that cleave the N-terminal two amino acids of proteins. There are >30 known substrates for DPPIV, the best characterized member of this family. Importantly the catalytic activity of DPPIV results in the conversion of agonist ligands into antagonist or non-functional proteins.In the context of our funded ERC project, we have provided the first in vivo evidence of DPPIV-mediated cleavage of the chemokine interferon-induced protein 10 (IP-10 or CXCL10) [Casrouge, JCI 2011]. These initial observations have recently been validated, conclusively demonstrating the ability to predict treatment failure in chronic HCV patients (p-value <0.001 for antagonist CXCL10 and negative predictive value = 93.5%).Based on the important role of DDPIV in disease pathogenesis and following from our findings, there are two ideas that we wish to develop further as proof of concept for ‘Functional Biomarkers’ in the management of patients. First, we wish to evaluate the market needs for developing a privately run SME, aimed at providing theragnostic testing useful for stratification of chronic HCV patients. We will also examine the potential value of applying these in vitro diagnostic (IVD) tools in other disease settings in which DPPIV and/or CXCL10 have been identified as a predictive biomarker. Second, we aim to extend our repertoire of assays to include other disease relevant DPPIV substrates.