A preliminary in vitro study into the use of IL-1Ra gene therapy for the inhibition of intervertebral disc degeneration.

作者: Christine L. Le Maitre , Anthony J. Freemont , Judith A. Hoyland

DOI: 10.1111/J.0959-9673.2006.00449.X

关键词: Genetic transferPathologyIn vitroIntervertebral discEx vivoGene expressionBiologyIntervertebral diskMolecular biologyViral vectorGenetic enhancement

摘要: Conventional therapies for low back pain (LBP) are purely symptomatic and do not target the cause of LBP, which in approximately 40% cases is caused by degeneration intervertebral disc (DIVD). Targeting to inhibit process would be a potentially valuable treatment LBP. There increasing evidence role IL-1 DIVD. A natural inhibitor exists, IL-1Ra, an ideal molecular inhibiting IL-1-mediated effects involved DIVD In this study, feasibility ex vivo gene transfer IL-1Ra IVD was investigated. Monolayer alginate cultures normal degenerate human (IVD) cells were infected with adenoviral vector carrying (Ad-IL-1Ra) protein production measured using enzyme-linked immunosorbent assay. The ability these also addition, Ad-IL-1Ra injected into tissue explants discs assessed. This demonstrated that both nucleus pulposus annulus fibrosus produced elevated levels prolonged time periods, resistant IL-1. When explants, expression increased maintained 2 weeks investigation. vitro study has shown use feasible therapy inhibition events during degeneration.

参考文章(58)
G R Burmester, S Kary, Anakinra: the first interleukin-1 inhibitor in the treatment of rheumatoid arthritis. International Journal of Clinical Practice. ,vol. 57, pp. 231- 234 ,(2003)
Krishnan Br, Interleukin-1 receptor antagonist gene therapy for arthritis. Current Opinion in Molecular Therapeutics. ,vol. 1, pp. 454- 457 ,(1999)
Herndon Jh, Kang R, Robbins Pd, Evans Ch, Muzzonigro Ts, Ghivizzani Sc, The Marshall R. Urist Young Investigator Award. Orthopaedic applications of gene therapy. From concept to clinic. Clinical Orthopaedics and Related Research. pp. 324- ,(2000)
Steven M. Leber, Masahito Yamagata, Joshua R. Sanes, Chapter 9 Gene Transfer Using Replication--Defective Retroviral and Adenoviral Vectors Methods in Cell Biology. ,vol. 51, pp. 161- 183 ,(1996) , 10.1016/S0091-679X(08)60628-7
Christine Le Maitre, Anthony J Freemont, Judith Hoyland, The role of interleukin-1 in the pathogenesis of human Intervertebral disc degeneration Arthritis Research & Therapy. ,vol. 7, pp. 1- 14 ,(2005) , 10.1186/AR1732
Timothy M. Ganey, Hans Meisel, A potential role for cell-based therapeutics in the treatment of intervertebral disc herniation. European Spine Journal. ,vol. 11, pp. 150- 158 ,(2002) , 10.1007/S00586-002-0494-7
C. Li, CANCER: DNA Damage, Deamidation, and Death Science. ,vol. 298, pp. 1346- 1347 ,(2002) , 10.1126/SCIENCE.1079168
Mike Sheppard, B. Rajendra Krishnan, Jean-Pierre Pelletier, In vivo transfer of interleukin-1 receptor antagonist gene in osteoarthritic rabbit knee joints: prevention of osteoarthritis progression. American Journal of Pathology. ,vol. 154, pp. 1159- 1169 ,(1999) , 10.1016/S0002-9440(10)65368-0
Ulf Müller-Ladner, Charles R Roberts, Barry N Franklin, Renate E Gay, Paul D Robbins, Christopher H Evans, Steffen Gay, Human IL-1Ra gene transfer into human synovial fibroblasts is chondroprotective. Journal of Immunology. ,vol. 158, pp. 3492- 3498 ,(1997)