title: Alternative for anti-TNF antibodies for arthritis treatment.
abstract: Tumor necrosis factor-α (TNF-α), a proinflammatory cytokine, plays a key role in the pathogenesis of many inflammatory diseases, including arthritis. Neutralization of this cytokine by anti-TNF-α antibodies has shown its efficacy in rheumatoid arthritis (RA) and is now widely used. Nevertheless, some patients currently treated with anti-TNF-α 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-α 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-α 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-α TFO modulates arthritis in vivo, thus providing proof-of-concept that it could be used as therapeutic tool for TNF-α-dependent inflammatory disorders.
authors.affiliation: UMR 7561 CNRS, Nancy Université Physiopathologie, Pharmacologie et Ingénierie Articulaires, Vandoeuvre lès Nancy, France.
authors.forename: Joseph
authors.initials: J
authors.lastname: Paquet
authors.forename: Christel
authors.initials: C
authors.lastname: Henrionnet
authors.forename: Astrid
authors.initials: A
authors.lastname: Pinzano
authors.forename: Jean-Baptiste
authors.initials: JB
authors.lastname: Vincourt
authors.forename: Pierre
authors.initials: P
authors.lastname: Gillet
authors.forename: Patrick
authors.initials: P
authors.lastname: Netter
authors.forename: Isabelle
authors.initials: I
authors.lastname: Chary-Valckenaere
authors.forename: Damien
authors.initials: D
authors.lastname: Loeuille
authors.forename: Jacques
authors.initials: J
authors.lastname: Pourel
authors.forename: Laurent
authors.initials: L
authors.lastname: Grossin
mesh_terms: D000818:Animals; D001168:Arthritis / Q000188:drug therapy* / Q000276:immunology; D001323:Autoantibodies / Q000276:immunology / Q000627:therapeutic use*; D002478:Cells, Cultured; D004195:Disease Models, Animal; D007167:Immunotherapy; D034741:RNA, Small Interfering / Q000235:genetics; D051381:Rats; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000276:immunology*
chemical_list: D001323:Autoantibodies; D034741:RNA, Small Interfering; D014409:Tumor Necrosis Factor-alpha