Defining Novel Targets for Intervention in Rheumatoid Arthritis: An Overview

Many and sometimes disparate immune and non-immune-mediated events contribute to the pathogenesis and progression of rheumatoid arthritis (RA). Despite recent advances in the development and implementation of diseasemodifying anti-rheumatic drugs and biological response modifiers for the treatment of RA, it remains vital that additional RA targets suitable for RA intervention be identified. Such novel targets for RA intervention would include, noninterleukin- 1 (non-IL-1)/non-tumor necrosis factor-α/non-IL-6 pro-inflammatory cytokines, growth factors that regulate angiogenesis as well as those required for synovial joint tissue repair. Proteins that are integral to the modulation of Tlymphocyte, B-lymphocyte, monocyte activity and synovial tissue apoptosis as well as complement, chemokines, adhesion molecules must also be considered. Because articular cartilage destruction and subchondral bone erosions are hallmarks of RA pathology, agents with the capability of modifying matrix metalloproteinases, tissue inhibitor of metalloproteinases and the family of enzyme proteins referred to as a disintegrin and metalloproteinases (ADAMs) or ADAMs with a thrombospondin motif (ADAMTS) as well as factors that regulate osteoclastogenesis and osteoclast activity such as receptor activator of nuclear factor-κB ligand (RANKL) should also be pursued.