Non-human primate model of collagen II-induced arthritis: a comprehensive system simulating human rheumatoid arthritis for evaluation of novel therapeutic candidates (THER5P.901)

Abstract

Abstract Non-human primate (NHP) model provides the advantage of closer phylogenetic relationship to human and high cross-reactivity to the human target specific biological molecules that do not react with rodent counterpart. PharmaLegacy has been dedicated in developing NHP inflammation models since 2009. Here, we report a NHP model of Collagen II induced Arthritis in Cynomolgus monkey, which developed similar symptoms as human RA in terms of body weight loss, clinical score lifting, joint swelling enlargement and rising PIP incidence. Terminal analysis by radiographic imaging and the multi-dimensional scaling for histopathology and histomorphometry on joints demonstrated similar characteristics of human RA joint deformity, including the significant cell infiltration, loss of proteoglycans (PG) in cartilage, Pannus development, osteophyte formation, loss of articular structure and bone erosion, well supporting for the arthritic disease. Therapeutic treatment with mAb HSF082D significantly reversed the above disease index. In a study of biomarkers profile in Serum or RA joint, CRP/IL-1β/IL-6/IL-17A/RANKL/GM-CSF were found to correlate with the arthritic severity at mRNA or protein levels. Th17 cell activities in synovial fluid were also detected.