GSK2394002 / GSK - LARVOL DELTA

REESTABLISHMENT OF THE ARGS PHARMACODYNAMIC, SERUM BIOMARKER. DEVELOPMENT OF A HIGH SENSITIVE CHEMILUMINESCENCE IMMUNOASSAY FOR DETECTION OF AGGRECANASE-GENERATED AGGRECAN FRAGMENTS (OARSI 2019) - "...Aggrecan is degraded by aggrecanases, such as ADAMTS-5, which are upregulated and activated in the pathogenesis of OA... This novel ARGS chemiluminescence immunoassay show good technical performance and high sensitivity toward assessment of ARGS in human and cyno serum samples. In addition, we confirmed that ARGS is released from cartilage in response to cytokines and inhibited by PCI. The assay may serve as a pharmacodynamics (PD) biomarker of aggrecanse inhibitors in the pre-clinical and clinical studies.Technical performance of the ARGS/G2 assay as serum measurementIntra-assay CV%2.36Inter-assay CV%15.9Low detection Limit (LDL) 23pMQuantifiable range 80-1390pMLinearity Dilution neat to 1:8Reference level in young healthy human donors (mean, range)289.7 (158.1-631.1) pM Reference level in cynos (mean, range)683.4 (139.9-1513) pM"

Biomarker • PK/PD data