Monoclonal antibody against envelope protein from Human Endogenous Retrovirus "W" (MSRV-ENV or Syncytin) inhibits TLR4-initated immunotoxicity cascade in human peripheral blood mononuclear cells and displays therapeutic effects in novel pre-clinical models for Multiple Sclerosis

• Published in: Journal of neurovirology 2007-01, Vol.13, p.112-112
• Main Authors: Perron, H, Sanhadji, K, Bernard, C, Touraine, J-L, Marche, P
• Format: Article
• Language: English
• Subjects: Human endogenous retrovirus
• ISSN: 1355-0284

HERV-W endogenous retroviral family encodes a powerful imunopathogenic envelope protein (MSRV-ENV or Syncytin), causing sequential activation of a pro-inflammatory and autoimmune cascade through initial interaction with Toll-Like receptor 4 (TLR4) on antigen-presenting cells, accompanied by gliotoxicity causing blood brain barrier (BBB) breakdown and further triggering superantigen (Sag)-like dysregulation of T-lymphocytes. The specific association of this protein with MS brain lesions post-mortem, as evidenced by independent immunohistological studies, its presence in about 75% of MS sera ex-vivo versus none in healthy controls (Cf. Epidemiology abstract) and its ability to reproduce the "EAE" MS animal model associated with demyelination and autoimmunity, has conducted us to select anti-ENV specific monoclonal antibodies (mAb) capable to block pathogenic effects of this protein in vitro. Further confirmation of therapeutic efficiency on clinical effects in vivo (animal models) was also pursued.