Clinical Responses to Gene Therapy in Joints of Two Subjects with Rheumatoid Arthritis

作者: Peter Wehling , Julio Reinecke , Axel W.A. Baltzer , Markus Granrath , Klaus P. Schulitz

DOI: 10.1089/HUM.2008.075

关键词:

摘要: This paper provides the first evidence of a clinical response to gene therapy in human arthritis. Two subjects with rheumatoid arthritis received ex vivo, intraarticular delivery interleukin-1 receptor antagonist (IL-1Ra) cDNA. To achieve this, autologous synovial fibroblasts were transduced retrovirus, MFG-IRAP, carrying IL-1Ra as transgene, or remained untransduced controls. Symptomatic metacarpophalangeal (MCP) joints injected control cells. Joints clinically evaluated on basis pain; circumference MCP joint 1 was also measured. After 4 weeks, underwent surgical synovectomy. There no adverse events either subject. The subject responded dramatically transfer, marked and rapid reduction pain swelling that lasted for entire weeks study. Remarkably, receiving cDNA protected from flares occurred during study period. Analysis RNA recovered after synovectomy revealed enhanced expression reduced matrix metalloproteinase-3 IL-1β. second swelling. Thus, transfer human, can be accomplished safely produce benefit, at least short term. Using this vivo procedure, transgene persisted within month. Further studies are warranted.

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