RESEARCH - Clinical response to gene therapy in two patients with RA

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Human Gene Therapy

doi:10.1089/hgt.2008.075

" Clinical responses to gene therapy in joints of two subjects with

rheumatoid arthritis " :

http://www.liebertonline.com/doi/pdfplus/10.1089/hgt.2008.075

This communication provides the first evidence of a clinical response

to gene therapy in human arthritis. Two subjects with rheumatoid

arthritis (RA) received ex vivo, intraarticular delivery of human

interleukin-1 receptor antagonist (IL-1Ra) cDNA. To achieve this,

autologous synovial fibroblasts were transduced with a retrovirus,

MFG-IRAP, carrying IL-1Ra as the transgene, or remained as

untransduced controls. Symptomatic metacarpophalangeal (MCP) joints

were injected with control or transduced cells. Joints were clinically

evaluated on the basis of pain; the circumference of MCP 1 was also

measured. After 4 weeks, joints underwent surgical synovectomy. There

were no adverse events in either subject. The first subject responded

dramatically to gene transfer, with a marked and rapid reduction in

pain and swelling that lasted for the entire 4 weeks of the study.

Remarkably, joints receiving IL-1Ra cDNA were protected from flares

that occurred during the study period. Analysis of RNA recovered after

synovectomy revealed enhanced expression of IL-1Ra and reduced

expression of matrix metalloproteinase-3 and IL-1beta. The second

subject also responded with reduced pain and swelling. Thus, gene

transfer to human, rheumatoid joints can be accomplished safely to

produce clinical benefit, at least in the short term. Using this ex

vivo procedure, the transgene persisted within the joint for at least

one month. Further clinical studies are warranted.

Not an MD