PMID- 21811249
OWN - NLM
STAT- MEDLINE
DCOM- 20120203
LR  - 20220311
IS  - 1525-0024 (Electronic)
IS  - 1525-0016 (Print)
IS  - 1525-0016 (Linking)
VI  - 19
IP  - 10
DP  - 2011 Oct
TI  - Alternative for anti-TNF antibodies for arthritis treatment.
PG  - 1887-95
LID - 10.1038/mt.2011.156 [doi]
AB  - Tumor necrosis factor-alpha (TNF-alpha), a proinflammatory cytokine, plays a key role in 
      the pathogenesis of many inflammatory diseases, including arthritis. 
      Neutralization of this cytokine by anti-TNF-alpha antibodies has shown its efficacy 
      in rheumatoid arthritis (RA) and is now widely used. Nevertheless, some patients 
      currently treated with anti-TNF-alpha remain refractory or become nonresponder to 
      these treatments. In this context, there is a need for new or complementary 
      therapeutic strategies. In this study, we investigated in vitro and in vivo 
      anti-inflammatory potentialities of an anti-TNF-alpha triplex-forming oligonucleotide 
      (TFO), as judged from effects on two rat arthritis models. The inhibitory 
      activity of this TFO on articular cells (synoviocytes and chondrocytes) was 
      verified and compared to that of small interfering RNA (siRNA) in vitro. The use 
      of the anti-TNF-alpha TFO as a preventive and local treatment in both acute and 
      chronic arthritis models significantly reduced disease development. Furthermore, 
      the TFO efficiently blocked synovitis and cartilage and bone destruction in the 
      joints. The results presented here provide the first evidence that gene targeting 
      by anti-TNF-alpha TFO modulates arthritis in vivo, thus providing proof-of-concept 
      that it could be used as therapeutic tool for TNF-alpha-dependent inflammatory 
      disorders.
FAU - Paquet, Joseph
AU  - Paquet J
AD  - UMR 7561 CNRS, Nancy Universite Physiopathologie, Pharmacologie et Ingenierie 
      Articulaires, Vandoeuvre les Nancy, France.
FAU - Henrionnet, Christel
AU  - Henrionnet C
FAU - Pinzano, Astrid
AU  - Pinzano A
FAU - Vincourt, Jean-Baptiste
AU  - Vincourt JB
FAU - Gillet, Pierre
AU  - Gillet P
FAU - Netter, Patrick
AU  - Netter P
FAU - Chary-Valckenaere, Isabelle
AU  - Chary-Valckenaere I
FAU - Loeuille, Damien
AU  - Loeuille D
FAU - Pourel, Jacques
AU  - Pourel J
FAU - Grossin, Laurent
AU  - Grossin L
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20110802
PL  - United States
TA  - Mol Ther
JT  - Molecular therapy : the journal of the American Society of Gene Therapy
JID - 100890581
RN  - 0 (Autoantibodies)
RN  - 0 (RNA, Small Interfering)
RN  - 0 (Tumor Necrosis Factor-alpha)
SB  - IM
MH  - Animals
MH  - Arthritis/*drug therapy/immunology
MH  - Autoantibodies/immunology/*therapeutic use
MH  - Cells, Cultured
MH  - Disease Models, Animal
MH  - *Immunotherapy
MH  - RNA, Small Interfering/genetics
MH  - Rats
MH  - Tumor Necrosis Factor-alpha/genetics/*immunology
PMC - PMC3188747
EDAT- 2011/08/04 06:00
MHDA- 2012/02/04 06:00
PMCR- 2012/10/01
CRDT- 2011/08/04 06:00
PHST- 2011/08/04 06:00 [entrez]
PHST- 2011/08/04 06:00 [pubmed]
PHST- 2012/02/04 06:00 [medline]
PHST- 2012/10/01 00:00 [pmc-release]
AID - S1525-0016(16)32781-2 [pii]
AID - 10.1038/mt.2011.156 [doi]
PST - ppublish
SO  - Mol Ther. 2011 Oct;19(10):1887-95. doi: 10.1038/mt.2011.156. Epub 2011 Aug 2.