A United States company is developing a gene therapy approach to blocking tumour necrosis factor (TNF) as a treatment for arthritis and other inflammatory diseases. Targeted Genetics Corporation is using its adeno-associated virus (AAV) vector technology to deliver the gene for TNF receptor-immunoglobulin Fc fusion protein (TNFR:Fc).
A single intra-articular administration of the gene into both rear ankle joints of arthritic rats resulted in a significant reduction of ankle and hind paw swelling, reported the company at a recent meeting of the American Society of Gene Therapy. A single intramuscular administration produced a similar effect and bioactive TNFR:Fc protein was readily detectable in the serum of treated rats 33 days after administration. The absence of a significant increase in serum TNFR:Fc protein levels following intra-articular administration suggested that local joint administration of the therapy was less likely to lead to systemic distribution of the TNF-a antagonist, said the company.
Commenting on the research, Dr Barrie Carter (research and development director, Targeted Genetics) said: "Recombinant TNF receptor-immunoglobulin Fc fusion protein has been shown to have a positive impact on the symptoms of RA by antagonising the function of TNF-a, a key component of the inflammatory response. We believe that the safety profile and long-term expression properties of our AAV vectors make them a logical approach to developing a gene-based delivery system for this important therapeutic protein." Dr Carter added that Targeted Genetics was "moving forward with the preclinical development of the human version of this construct."
Recombinant TNFR:Fc, etanercept (Enbrel), was recently launched as an arthritis therapy in the UK by Wyeth Laboratories (PJ, June 3, p860).