TREEting Rheumatoid Arthritis

Abstract

Biomaterials Rheumatoid arthritis is an autoimmune inflammatory disorder that can cause swelling of the joints, cartilage degradation, and eventual bone erosion. The immunological processes are controlled by a set of cytokines (cell signaling molecules) that trigger an inflammatory response, diminish anti-inflammatory responses, and promote the differentiation of monocytes into osteoclasts. Current treatments, based on monoclonal antibodies and soluble receptors, typically target only the proinflammatory cytokines. Hayder et al. synthesized dendrimers—highly branched tree-like polymers—in which the outer branches were capped with azabisphosphonate (ABP), which has been shown to selectively target monocytes in culture. These dendrimers were tested in mice with a deficiency in the interleukin-1 receptor antagonist and in mice undergoing K/BxN serum transfer, which are two established inflammatory arthritis models. At the highest doses tested (1 and 10 mg/kg), intravenous injections completely suppressed inflammation, as evidenced by a decrease in paw swelling and little or no damage to the synovial fluid and cartilage in the ankle joints. Further tests using ex vivo human synovial tissue and human peripheral blood monocytes in vitro showed that the ABP dendrimers prevented the conversion of monocytes into osteoclasts. Because the dendrimers promote anti-inflammatory responses in addition to preventing bone loss, they may prove more effective than current treatments for rheumatoid arthritis. Sci. Transl. Med. 3 , 81ra35 (2011).