Gene therapy for rheumatoid arthritis

Abstract

Rheumatoid arthritis (RA) is a disabling, painful disorder affecting 1% of the world’s population. Although the aetiology of RA remains unknown, recent advances in understanding its pathophysiology have led to the characterisation of several proteins whose activities may be anti-arthritic. Clinical application of such proteins has greatly improved the treatment of RA, but the disease remains incurable and difficult to manage in a substantial number of patients. Thus, there are continued efforts to develop new therapeutic strategies. Because RA is a chronic condition, effective treatment will probably require the presence of therapeutic agents for extended periods of time. In the case of proteins, this is problematic. Gene therapy may offer a solution to this problem. Experimental studies have confirmed the feasibility, efficacy and safety of gene therapy for the treatment of animal models of arthritis. Several different approaches have shown promise in this regard, including gene transfer to the synovial lining cells of individual joints and the systemic delivery of genes to extra-articular locations. One unexpected finding has been the ‘contralateral effect’ in which gene delivery to one joint of an animal with polyarticular disease leads to improvement of multiple joints. Investigation of this phenomenon has led to interest in cell trafficking and the genetic modification of antigen-presenting cells (APC). The first Phase I clinical trial tested the feasibility and safety of ex vivo gene transfer to the synovial lining of human joints. This clinical trial has been successfully completed and two other Phase I trials are in progress. A Phase II study is now being planned to investigate the efficacy of gene transfer to the joints of patients with early stage RA.

• contralateral effect
• gene therapy
• IL-1 receptor antagonist
• rheumatoid arthritis