Editorial [Hot-Topic: Molecular Mechanisms in Rheumatic Diseases:Rationale for Novel Drug Development (Guest Editor: Charles J. Malemud)]

Novel therapies for the treatment of rheumatoid arthritis (RA) appear to be on the horizon. Any advances in the development of novel therapeutics for RA will only be made possible as a result of our improved understanding of how immune-mediated inflammation contributes to the pathogenesis and progression of the RA disease process. Thus, recent advances in unraveling the way in which ‘cross-talk’ between intracellular signaling pathways contributes to RA pathology have resulted in the recognition that only through the suppression of multiple signal transduction pathways can amelioration of disease activity occur in human RA. In that regard, several intracellular protein kinase small molecule inhibitors are now being evaluated in human RA clinical trials. In addition, development of novel computational strategies combined with the use of proteomic databases have now been employed to enhance the rationale design of small molecule inhibitors that have the potential to be added to the armamentarium of already existing RA therapies. Finally, this research has also resulted in an improved design of small molecules which have the capacity to interfere with pro-inflammatory cytokine-induced gene expression to dampen the RA inflammatory response.