Biochemical markers and the FDA Critical Path: How biomarkers may contribute to the understanding of pathophysiology and provide unique and necessary tools for drug development

Abstract

The aim of this review is to discuss the potential usefulness of a novel class of biochemical markers, neoepitopes, in the context of the US Food and Drug Administration (FDA) Critical Path Initiative, which emphasizes biomarkers of safety and efficacy as areas of pivotal interest. Examples of protein degradation fragments--neoepitopes--that have proven useful for research on bone and cartilage are collagen type I and collagen type II degradation products, respectively. These markers have utility in the translational approach, as they can be used to estimate safety and efficacy in both preclinical models and clinical settings. Biochemical markers of tissue degradation may provide optimal tools, which in combination with other techniques, prove essential to drug discovery and development.

Extracellular Matrix Remodeling: The Common Denominator in Connective Tissue DiseasesPossibilities for Evaluation and Current Understanding of the Matrix as More Than a Passive Architecture, but a Key Player in Tissue Failure

“…Figure 3 depicts a handful of different types of PTMs. Some have been identified and used as biochemical markers as a measure of the disease activity, 272 but also as contributions to disease process, 17 as they change the functionality of the proteins.…”

Serum Markers of Liver Fibrosis: Combining the BIPED Classification and the Neo-Epitope Approach in the Development of New Biomarkers

“…The main approached taken are an unbiased proteomic approach involving a range of powerful techniques [66,130], and a more simple hypothesis driven approach [57]. Each approach provide advantages and drawback, however a deeper discussion is out of the current scope.…”

“…Particular emphasis should be directed to whether novel markers may be a diagnostic or prognostic marker [57]. Even though the combined approached with proteases degradation fragments may increase the accuracy of the biomarker, the exact tissue distribution and contribustion deserves attention to obtain maximal disease accuracy and assay precision.…”

“…have been shown to correlate with the number of affected sites, such as collagen type II degradation markers and number of affected joints in OA [82], tissue specificity and pathological relation must be carefully evaluated, possible by application of the BIPED criteria [7,57]. Particular emphasis should be directed to whether novel markers may be a diagnostic or prognostic marker [57].…”

Rheumatoid Arthritis: A Case for Personalized Health Care?

“…The well-recognized complexity of drug development is at least in part due to the heterogeneity of the underlying disease observed within any patient population. PHC has often been suggested as a solution to this complexity (2), but the majority of examples of successful PHC are currently drawn from the oncology field and, as such, reflect a relatively simplistic concept of therapeutic stratification based on the targeting of constitutively activated pathways in an oligogenic model of disease. Conversely, reportable successes for PHC in the field of polygenic disease are few and far between.…”