EDITORIAL - Arthritis gene therapy trials reach Phase II

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Journal of Rheumatology

April 2010

Editorial

Arthritis Gene Therapy Trials Reach Phase II

Arthritis has been on the gene therapy agenda for about 20 years1.

Despite its impressive preclinical track record of efficacy and safety

in animal models (as reviewed5,6), progress in carrying out clinical

trials has been painfully slow4. The literature contains only 2 small

Phase I studies3,4 and a report of 2 subjects who experienced

symptomatic relief following gene transfer7. The Phase I/II trial

described by Mease, et al in this issue of The Journal8 is thus very

much to be welcomed. Not only does it greatly increase the number of

subjects who have received gene therapy for arthritis, but it is also

the first trial to address efficacy in a substantial fashion.

Although there are several different strategies for using genes as

therapeutic agents in arthritis, by far the most progress has been

made with the approach of delivering genes locally to individual

diseased joints2,3. There are a number of reasons for this. Not only

was it the first arthritis gene therapy strategy to be proposed1, but

also, by enabling sustained, endogenous, intraarticular synthesis of

therapeutic gene products in selected joints, local delivery achieves

something that no other technology can accomplish. Moreover,

expressing the gene product intraarticularly minimizes exposure of

non-target sites, thereby reducing the potential for unwanted side

effects. The smaller requirements of local, rather than systemic,

treatment also lower costs, especially as a successful gene therapy

will require infrequent redosing. The burden of treating multiple

joints individually in patients with rheumatoid arthritis (RA) may be

less than first thought, following the discovery that the genetic

treatment of just one joint in animals with polyarticular disease

secures improvement in additional joints on the same individual9. The

degree to which suppression of intraarticular disease mitigates

extraarticular manifestations of RA remains to be determined.

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Read the full editorial here:

http://jrheum.org/content/37/4/683.full

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