Arthritis gene therapy's first death

Table 2 Human clinical trials of arthritis gene therapy

Transgene	Vector, ex vivo/in vivo	Phase	Principal investigator, institution/sponsor	OBA Protocol Number	Status	n
IL-1 receptor antagonist	Retrovirus, ex vivo	I	Evans and Robbins, University of Pittsburgh, USA	9406-074	Closed	9
IL-1 receptor antagonist	Retrovirus, ex vivo	I	Wehling, University of Düsseldorf, Germany	Not applicable	Closed	2
HSV-tk^a	Plasmid, in vivo	I	Roessler, University of Michigan, USA	9802-237	Closed	1
TNFR:Fc fusion protein (etanercept)	AAV, in vivo	I	Mease, Targeted Genetics Corp., USA	0307-588	Closed	15
TGFβ₁	Retrovirus, ex vivo	I	Ha, Kolon Life Sciences, Korea	Not applicable	Open	12
TGFβ₁	Retrovirus, ex vivo	I	Mont, TissueGene Inc., USA	0307-594	Open	4
TNFR:Fc fusion protein (etanercept)	AAV, in vivo	I/II	Mease, Targeted Genetics Corp., USA	0504-705	Enrolled. Clinical hold lifted by FDA in December 2007	127

All of these trials target rheumatoid arthritis except for the TissueGene and Kolon trials, which target osteoarthritis. The Targeted Genetics Corp. trial can also recruit subjects with psoriatic arthritis and ankylosing spondylitis. A phase I study injecting NF-κB decoy oligonucleotides is underway at the University of Osaka in Japan (principal investigator: Tomita). This study is not included because it is not strictly gene therapy. Also omitted for the same reason are two trials using TNF antisense RNA [14]. ^aWhen expressed in conjunction with ganciclivir administration, herpes simplex virus thymidine kinase (HSV-tk) kills synovial cells and produces a synovectomy. AAV, adeno-associated virus; FDA, Food and Drug Administration; n, number of subjects in study; OBA, Office of Biotechnology Activities; TGFβ₁, transforming growth factor beta 1; TNFR:Fc, tumor necrosis factor receptor:Fc domain of immunoglobulin fusion protein.

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