The Analytical Aspects and Regulatory Challenges of Biomarker Discovery: Examples from the Field of Neurodegeneration

Drug discovery is guided by theories regarding disease pathogenesis, and biomarkers are the essential analytical tools used to translate those theories into clinical experiments. Biomarkers can be used to expedite clinical trials by permitting selection of the most uniform and responsive patient population, by reporting on target engagement of a particular therapeutic mechanism, and by permitting measurement of biochemical or physiological correlates of disease mechanism with end points that may be more sensitive, immediate, or statistically robust than phenotypic or behavioral changes. Biomarker discovery necessarily begins with an analytically validated assay for an analyte, which is later qualified by demonstrating its utility in some context of disease and therapeutic state. Ultimately, just as with the drug discovery process as a whole, successful biomarker discovery and development depends upon a clear understanding of the disease process. This article reviews the challenges of biomarker discovery with an emphasis on fluid biomarkers in neurodegeneration.