NDLI: Gene transfer to human joints: Progress toward a gene therapy of arthritis

Content Provider	PubMed Central
Author	Evans, Christopher H. Robbins, Paul D. Ghivizzani, Steven C. Wasko, Mary Chester Tomaino, Matthew M. Kang, Richard Muzzonigro, Thomas A. Vogt, Molly Elder, Elaine M. Whiteside, Theresa L. Watkins, Simon C. Herndon, James H.
Copyright Year	2005
Abstract	This article describes the clinical application of gene therapy to a nonlethal disease, rheumatoid arthritis (RA). Intraarticular transfer of IL-1 receptor antagonist (IL-1Ra) cDNA reduces disease in animal models of RA. Whether this procedure is safe and feasible in humans was addressed in a phase I clinical study involving nine postmenopausal women with advanced RA who required unilateral sialastic implant arthroplasty of the 2nd-5th metacarpophalangeal (MCP) joints. Cultures of autologous synovial fibroblasts were established and divided into two. One was transduced with a retrovirus carrying IL-1Ra cDNA; the other provided untransduced, control cells. In a dose escalation, double-blinded fashion, two MCP joints were injected with transduced cells, and two MCP joints received control cells. One week later, injected joints were resected and examined for evidence of successful gene transfer and expression by using RT-PCR, ex vivo production of IL-1Ra, in situ hybridization, and immunohistochemistry. All subjects tolerated the protocol well, without adverse events. Unlike control joints, those receiving transduced cells gave positive RT-PCR signals. Synovia that were recovered from the MCP joints of intermediate and high dose subjects produced elevated amounts of IL-1Ra (P = 0.01). Clusters of cells expressing high levels of IL-1Ra were present on synovia of transduced joints. No adverse events occurred. Thus, it is possible to transfer a potentially therapeutic gene safely to human rheumatoid joints and to obtain intraarticular, transgene expression. This conclusion justifies additional efficacy studies and encourages further development of genetic approaches to the treatment of arthritis and related disorders.
Related Links	http://dx.doi.org/10.1073/pnas.0502854102
Ending Page	8703
Page Count	6
Starting Page	8698
File Format	PDF
ISSN	00278424
e-ISSN	10916490
Journal	Proceedings of the National Academy of Sciences of the United States of America
Issue Number	24
Volume Number	102
Language	English
Publisher	National Academy of Sciences
Publisher Date	2005-06-14
Access Restriction	Open
Rights Holder	National Academy of Sciences
Subject Keyword	General Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Multidisciplinary

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