tailieunhanh - Báo cáo y học: " Gene therapy in animal models of rheumatoid arthritis: are we ready for the patients"

Tuyển tập các báo cáo nghiên cứu về y học được đăng trên tạp chí y học General Psychiatry cung cấp cho các bạn kiến thức về ngành y đề tài: Gene therapy in animal models of rheumatoid arthritis: are we ready for the patients? | Available online http content 6 5 183 Review Gene therapy in animal models of rheumatoid arthritis are we ready for the patients Fons AJ van de Loo Ruben L Smeets and Wim B van den Berg Rheumatology Research and Advanced Therapeutics Department of Rheumatology University Medical Center Nijmegen Nijmegen Center for Molecular Life Sciences Nijmegen The Netherlands Corresponding author FAJ van de Loo Received 7 May 2004 Revisions requested 17 Jun 2004 Revisions received 21 Jun 2004 Accepted 21 Jun 2004 Published 29 July 2004 Arthritis Res Ther 2004 6 183-196 DOI ar1214 2004 BioMed Central Ltd Abstract Rheumatoid arthritis RA is a chronic inflammatory disease of the synovial joints with progressive destruction of cartilage and bone. Anti-tumour necrosis factor-a therapies . soluble tumour necrosis factor receptors ameliorate disease in 60-70 of patients with RA. However the need for repeated systemic administration of relatively high doses in order to achieve constant therapeutic levels in the joints and the reported side effects are downsides to this systemic approach. Several gene therapeutic approaches have been developed to ameliorate disease in animal models of arthritis either by restoring the cytokine balance or by genetic synovectomy. In this review we summarize strategies to improve transduction of synovial cells to achieve stable transgene expression using integrating viruses such as adeno-associated viruses and to achieve transcriptionally regulated expression so that drug release can meet the variable demands imposed by the intermittent course of RA. Evidence from animal models convincingly supports the application of gene therapy in RA and the feasibility of gene therapy was recently demonstrated in phase I clinical trials. Keywords arthritis cytokines gene therapy genetic synovectomy transcriptional regulation Introduction Rheumatoid arthritis RA is an autoimmune disease that is characterized by .