Osteoarthritis gene therapy

Christopher H Evans, J. N. Gouze, E. Gouze, P. D. Robbins, S. C. Ghivizzani

Research output: Contribution to journalArticle

104 Citations (Scopus)

Abstract

Osteoarthritis (OA) is the Western world's leading cause of disability. It is incurable, costly and responds poorly to treatment. This review discusses strategies for treating OA by gene therapy. As OA affects a limited number of weight-bearing joints and has no major extra-articular manifestations, it is well suited to local, intra-articular gene therapy. Possible intra-articular sites of gene transfer include the synovium and the cartilage. Most experimental progress has been made with gene transfer to synovium, a tissue amenable to genetic modification by a variety of vectors, using both in vivo and ex vivo protocols. The focus so far has been upon the transfer of genes whose products enhance synthesis of the cartilaginous matrix, or inhibit its breakdown, although there is certainly room for alternative targets. It is possible to build a convincing case implicating interleukin-1 (IL-1) as a key mediator of cartilage loss in OA, and the therapeutic effects of IL-1 receptor anatagonist (IL-1Ra) gene transfer have been confirmed in three different experimental models of OA. As transfer of IL-1Ra cDNA to human arthritic joints has already been accomplished safely, we argue that clinical studies of intra-articular IL-1Ra gene transfer in OA are indicated and should be funded. Of the available vector systems, recombinant adeno-associated virus may provide the best combination of safety with in vivo delivery using current technology.

Original languageEnglish (US)
Pages (from-to)379-389
Number of pages11
JournalGene Therapy
Volume11
Issue number4
DOIs
StatePublished - Feb 2004
Externally publishedYes

Fingerprint

Osteoarthritis
Genetic Therapy
Joints
Interleukin-1 Receptors
Synovial Membrane
Genes
Cartilage
Dependovirus
Western World
Weight-Bearing
Therapeutic Uses
Interleukin-1
Arthritis
Theoretical Models
Complementary DNA
Technology
Safety

Keywords

  • Arthritis
  • Cartilage
  • Clinical trial
  • IL-1Ra
  • Joint
  • Synovium

ASJC Scopus subject areas

  • Genetics

Cite this

Evans, C. H., Gouze, J. N., Gouze, E., Robbins, P. D., & Ghivizzani, S. C. (2004). Osteoarthritis gene therapy. Gene Therapy, 11(4), 379-389. https://doi.org/10.1038/sj.gt.3302196

Osteoarthritis gene therapy. / Evans, Christopher H; Gouze, J. N.; Gouze, E.; Robbins, P. D.; Ghivizzani, S. C.

In: Gene Therapy, Vol. 11, No. 4, 02.2004, p. 379-389.

Research output: Contribution to journalArticle

Evans, CH, Gouze, JN, Gouze, E, Robbins, PD & Ghivizzani, SC 2004, 'Osteoarthritis gene therapy', Gene Therapy, vol. 11, no. 4, pp. 379-389. https://doi.org/10.1038/sj.gt.3302196
Evans CH, Gouze JN, Gouze E, Robbins PD, Ghivizzani SC. Osteoarthritis gene therapy. Gene Therapy. 2004 Feb;11(4):379-389. https://doi.org/10.1038/sj.gt.3302196
Evans, Christopher H ; Gouze, J. N. ; Gouze, E. ; Robbins, P. D. ; Ghivizzani, S. C. / Osteoarthritis gene therapy. In: Gene Therapy. 2004 ; Vol. 11, No. 4. pp. 379-389.
@article{44a723aa908f43ffa10c8e14b8a1d278,
title = "Osteoarthritis gene therapy",
abstract = "Osteoarthritis (OA) is the Western world's leading cause of disability. It is incurable, costly and responds poorly to treatment. This review discusses strategies for treating OA by gene therapy. As OA affects a limited number of weight-bearing joints and has no major extra-articular manifestations, it is well suited to local, intra-articular gene therapy. Possible intra-articular sites of gene transfer include the synovium and the cartilage. Most experimental progress has been made with gene transfer to synovium, a tissue amenable to genetic modification by a variety of vectors, using both in vivo and ex vivo protocols. The focus so far has been upon the transfer of genes whose products enhance synthesis of the cartilaginous matrix, or inhibit its breakdown, although there is certainly room for alternative targets. It is possible to build a convincing case implicating interleukin-1 (IL-1) as a key mediator of cartilage loss in OA, and the therapeutic effects of IL-1 receptor anatagonist (IL-1Ra) gene transfer have been confirmed in three different experimental models of OA. As transfer of IL-1Ra cDNA to human arthritic joints has already been accomplished safely, we argue that clinical studies of intra-articular IL-1Ra gene transfer in OA are indicated and should be funded. Of the available vector systems, recombinant adeno-associated virus may provide the best combination of safety with in vivo delivery using current technology.",
keywords = "Arthritis, Cartilage, Clinical trial, IL-1Ra, Joint, Synovium",
author = "Evans, {Christopher H} and Gouze, {J. N.} and E. Gouze and Robbins, {P. D.} and Ghivizzani, {S. C.}",
year = "2004",
month = "2",
doi = "10.1038/sj.gt.3302196",
language = "English (US)",
volume = "11",
pages = "379--389",
journal = "Gene Therapy",
issn = "0969-7128",
publisher = "Nature Publishing Group",
number = "4",

}

TY - JOUR

T1 - Osteoarthritis gene therapy

AU - Evans, Christopher H

AU - Gouze, J. N.

AU - Gouze, E.

AU - Robbins, P. D.

AU - Ghivizzani, S. C.

PY - 2004/2

Y1 - 2004/2

N2 - Osteoarthritis (OA) is the Western world's leading cause of disability. It is incurable, costly and responds poorly to treatment. This review discusses strategies for treating OA by gene therapy. As OA affects a limited number of weight-bearing joints and has no major extra-articular manifestations, it is well suited to local, intra-articular gene therapy. Possible intra-articular sites of gene transfer include the synovium and the cartilage. Most experimental progress has been made with gene transfer to synovium, a tissue amenable to genetic modification by a variety of vectors, using both in vivo and ex vivo protocols. The focus so far has been upon the transfer of genes whose products enhance synthesis of the cartilaginous matrix, or inhibit its breakdown, although there is certainly room for alternative targets. It is possible to build a convincing case implicating interleukin-1 (IL-1) as a key mediator of cartilage loss in OA, and the therapeutic effects of IL-1 receptor anatagonist (IL-1Ra) gene transfer have been confirmed in three different experimental models of OA. As transfer of IL-1Ra cDNA to human arthritic joints has already been accomplished safely, we argue that clinical studies of intra-articular IL-1Ra gene transfer in OA are indicated and should be funded. Of the available vector systems, recombinant adeno-associated virus may provide the best combination of safety with in vivo delivery using current technology.

AB - Osteoarthritis (OA) is the Western world's leading cause of disability. It is incurable, costly and responds poorly to treatment. This review discusses strategies for treating OA by gene therapy. As OA affects a limited number of weight-bearing joints and has no major extra-articular manifestations, it is well suited to local, intra-articular gene therapy. Possible intra-articular sites of gene transfer include the synovium and the cartilage. Most experimental progress has been made with gene transfer to synovium, a tissue amenable to genetic modification by a variety of vectors, using both in vivo and ex vivo protocols. The focus so far has been upon the transfer of genes whose products enhance synthesis of the cartilaginous matrix, or inhibit its breakdown, although there is certainly room for alternative targets. It is possible to build a convincing case implicating interleukin-1 (IL-1) as a key mediator of cartilage loss in OA, and the therapeutic effects of IL-1 receptor anatagonist (IL-1Ra) gene transfer have been confirmed in three different experimental models of OA. As transfer of IL-1Ra cDNA to human arthritic joints has already been accomplished safely, we argue that clinical studies of intra-articular IL-1Ra gene transfer in OA are indicated and should be funded. Of the available vector systems, recombinant adeno-associated virus may provide the best combination of safety with in vivo delivery using current technology.

KW - Arthritis

KW - Cartilage

KW - Clinical trial

KW - IL-1Ra

KW - Joint

KW - Synovium

UR - http://www.scopus.com/inward/record.url?scp=1342285045&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=1342285045&partnerID=8YFLogxK

U2 - 10.1038/sj.gt.3302196

DO - 10.1038/sj.gt.3302196

M3 - Article

VL - 11

SP - 379

EP - 389

JO - Gene Therapy

JF - Gene Therapy

SN - 0969-7128

IS - 4

ER -