EFFECTS OF IV ADMINISTERED AMG 108 IN CHIMPANZEES

点击翻译按钮获取中文摘要

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. This study will be testing a monoclonal antibody designed against the interleukin-1 receptor. Interleukin-1 is a key cytokine in inflammatory disorders and its inhibition has been demonstrated to provide therapeutic benefit for rheumatoid arthritis patients. As such KineretTM, a recombinant IL-1 receptor antagonist, it currently marketed for the treatment of rheumatoid arthritis. AMG 108 does not cross react with the IL-1 receptor of any rodent or lower primate species. In order for any meaningful safety studies to be carried out in animals, the animal species selected must retain biological activity against AMG 108. Only chimps and humans have demonstrated a biological response (binding to the IL-1 receptor) to AMG 108. The chimp, therefore, is the only primate species that may be used to evaluate the potential toxicity of AMG 108 prior to its introduction into humans. The effects of IL-1 inhibition through an antibody are largely unknown and data from this study will be useful in filling that knowledge gap as well as enabling the design of more appropriate clinical trials.