Gene therapy for rheumatoid arthritis.
Rheumatoid arthritis (RA) is a severe autoimmune systemic disease. Chronic synovial inflammation results in destruction of the joints. No conventional treatment is efficient in RA. Gene therapy of RA targets mainly the players of inflammation or articular destruction: TNF-alpha or IL-1 blocking agents (such as anti-TNF-alpha monoclonal antibodies, soluble TNF-alpha receptor, type II soluble receptor of IL-1, IL-1 receptor antagonist), antiinflammatory cytokines (such as IL-4, IL-10, IL-1), and growth factors. In this polyarticular disease, the vector expressing the therapeutic protein can be administered as a local (intra-articular injection) or a systemic treatment (extra-articular injection). All the main vectors have been used in experimental models, including the more recent lentivirus and adeno-associated virus. Ex vivo gene transfer was performed with synovial cells, fibroblasts, T cells, dendritic cells, and different cells from xenogeneic origin. In vivo gene therapy is simpler, although a less controlled method. Clinical trials in human RA have started with ex vivo retrovirus-expressing IL-1 receptor antagonists and have demonstrated the feasibility of the strategy of gene therapy. The best target remains to be determined and extensive research has to be conducted in preclinical studies.
Bessis
Natacha
N
UPRES EA-3408 (Université Paris 13) and Service de Rhumatologie (CHU Avicenne, AP-HP), Bobigny, France. bessis@smbh.univ-paris13.fr
Doucet
Christelle
C
Cottard
Virginie
V
Douar
Anne-Marie
AM
Firat
Hüseyin
H
Jorgensen
Christian
C
Mezzina
Mauro
M
Boissier
Marie-Christophe
MC
D001172:Arthritis, Rheumatoid / Q000628:therapy*; D002986:Clinical Trials as Topic; D015316:Genetic Therapy; D005822:Genetic Vectors; D006801:Humans; D007249:Inflammation