Gene Therapy for Rheumatoid Arthritis

Margriet   J.   Vervoordeldonk; Janik      Adriaansen; Frits   J.   Fallaux; Paul   P.   Tak

doi:10.2174/187152307780598063

Abstract

Rheumatoid arthritis (RA) is a chronic inflammatory disease characterised by persistent joint swelling and progressive destruction of cartilage and bone. The primary manifestations are pain, swelling, and limited joint motility due to inflammation of the synovial membrane. In addition to conventional therapies, biologicals targeting cytokines and their receptors have proven useful as specific therapies for RA. Although these new biologicals have improved treatment to a certain extent and do provide proof of principle for targeted therapies, many patients continue to experience inflammation in one or more joints and repeated injections of the recombinant protein are needed for a long-term therapeutic effect. Gene therapy can provide stable, long-term expression of therapeutic proteins at the site of inflammation and thereby improve the treatment of RA and reduce costs related to the treatment with biologicals. Several gene therapy approaches have been developed and tested in animal models of arthritis. Currently a large number of ongoing studies are attempting to improve the efficacy and safety of vectors that are promising for gene therapeutic applications in humans. In addition, studies have been initiated to select new therapeutic candidate genes for the treatment of RA. After almost 20 years of preclinical research the first clinical trials in RA patients have been performed or are ongoing. This review describes the current status of the most promising vectors and therapeutic genes for gene therapy in RA.

Keywords: Rheumatoid arthritis, gene therapy, vectors, adeno-associated virus, lentivirus, adenovirus, animal models, therapeutic genes