Highly Multiplexed Proteomic Analysis as a translational tool: Implications for useful biomarker discovery and early clinical development.
Stephen Williams1,*, Britta Singer1, Bob Mehler1, Timothy Bauer1, David Sterling1, Ed Brody1
1SomaLogic Inc, Boulder, United States
Introduction: A significant challenge in early clinical development of new therapeutics relates to the low predictive value of biomarkers derived from pre-clinical model systems in human disease.
Objectives: One approach to this issue is through the use of a rapid, highly multiplexed, quantitative assay solution targeted at human proteins and cross-species homologs.
Methods: SOMAscan™ , a high-throughput, multiplexed proteomic assay (>1100 protein analytes), is capable of simultaneously measuring proteins from small volumes of biological samples such as plasma, tissue or cell culture and has been successfully applied to clinical studies and multiple non-clinical model systems. Two independent studies were conducted using the SOMAscan™ assay.
Results: In a mouse model of aging, 13 proteins were indentified that discriminated between young and old mice, and treatment with one of these proteins (GDF-11) was successful in mitigating the observed age-related cardiac hypertrophy (Loffredo et al 2013). Using the same SOMAscan™ platform, 12 proteins were identified as independent predictors of subsequent cardiovascular events in 986 CVD patients (Ganz et al pending). Comparison of primary findings between the two studies identified a deficiency of at least one protein (GDF-11) that was related to both cardiac remodeling as well as increased cardiovascular event risk. These observations have led to subsequent therapeutic investigations of GDF-11.
Conclusion: Although circumstantial, these data suggest the potential for cross-species SOMAscan™ as a unique approach and tool in the context of translational medicine. The ability to rapidly discover human biomarker homologs in pre-clinical systems and extend those discoveries to early clinical applications, as biomarkers or potential new therapeutic targets , poses a significant advance towards streamlining and potentially de-risking early clinical development.
Keywords: Biomarker, Biomarker development