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Modeling human arthritic diseases in nonhuman primates

DOI: 10.1186/ar1773

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Rheumatoid arthritis (RA) is a chronic inflammatory disease of unknown etiology [1,2]. Once established, immune reactions against joint components contribute significantly to the pathological hallmarks of the disease, being synovial hyperplasia (pannus formation) and a variable degree of destruction and remodeling of joint cartilage and bone. RA affects approximately 1% of people in Western countries, with a 2:1 prevalence in females over males. The ageing societies in the developed countries create a growing need for safer and more effective therapies to treat chronic diseases such as RA. The advent of biotechnology has fuelled the search for drugs that act more specifically to overcome the considerable side effects of nonspecific anti-inflammatory and immunosuppressive drugs. Especially for immune-mediated diseases, biotechnology-based therapies have a great therapeutic potential. The preclinical development of immunomodulatory compounds often begins with an observation in vitro, after which proof of therapeutic principle is obtained in animal models, usually in inbred strains of rats or mice.Unfortunately, the promising effects of new therapeutics observed in rodents are often not reproduced on testing in patients. There is a growing awareness that the evolutionary gap between inbred rodent strains and the human population is too wide for direct translation of data from rodents to humans [3]. Because of the closer evolutionary and immunological proximity to humans, nonhuman primates may help to bridge this gap [4-6]. Trans-species antigen presentation of human antigen-presenting cells to rhesus T cells and vice versa [7,8] nicely illustrates the immunological proximity of rhesus monkeys and humans [9-11].It is of critical importance for preclinical safety testing that the selected animal model is sensitive to the pharmacological action of the tested drug and that the tissue distribution and pharmacological properties of the molecules targeted by the treatment are


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