Michel Vierboom1, Elia Breedveld, Ivanela Kondova, Bert A 't Hart. 1. Biomedical Primate Research Centre, Department of Immunobiology, PO Box 3306, 2280 GH Rijswijk, The Netherlands +31 15 284 2500 ; +31 15 284 2600 ; vierboom@bprc.nl.
Abstract
BACKGROUND: The broad immunological gap between inbred SPF-raised strains of mice and rats and the diverse rheumatoid arthritis (RA) patient population limits the predictive value of the existing disease models for clinical success of new therapies, in particular for those using highly specific biologicals. OBJECTIVE: This review argues that because of their closer immunological and physiological proximity to patients, disease models in non-human primates (NHPs) may bridge this gap and help reduce the failure of many (± 80%) new therapies in clinical trials. In various research areas, NHPs are an accepted intermediate between disease models in rodents and the ultimate introduction for clinical use in patients. However, with the exception of transplantation, this is not the case for immune-mediated inflammatory disorders, such as RA, although useful preclinical models are being developed. METHOD: The validity and use of the rhesus monkey model of collagen-induced arthritis as a preclinical RA model is reviewed. The discussion comprises present genetic and immunological aspects, biomarkers, and an overview of published preclinical therapy evaluations. CONCLUSION: It is time to consider the use of NHPs with a greater evolutionary proximity to humans as models for preclinical evaluation of new human-specific drugs for arthritic disease.
BACKGROUND: The broad immunological gap between inbred SPF-raised strains of mice and rats and the diverse rheumatoid arthritis (RA) patient population limits the predictive value of the existing disease models for clinical success of new therapies, in particular for those using highly specific biologicals. OBJECTIVE: This review argues that because of their closer immunological and physiological proximity to patients, disease models in non-human primates (NHPs) may bridge this gap and help reduce the failure of many (± 80%) new therapies in clinical trials. In various research areas, NHPs are an accepted intermediate between disease models in rodents and the ultimate introduction for clinical use in patients. However, with the exception of transplantation, this is not the case for immune-mediated inflammatory disorders, such as RA, although useful preclinical models are being developed. METHOD: The validity and use of the rhesus monkey model of collagen-induced arthritis as a preclinical RA model is reviewed. The discussion comprises present genetic and immunological aspects, biomarkers, and an overview of published preclinical therapy evaluations. CONCLUSION: It is time to consider the use of NHPs with a greater evolutionary proximity to humans as models for preclinical evaluation of new human-specific drugs for arthritic disease.