title: MSRV envelope protein is a potent, endogenous and pathogenic agonist of human toll-like receptor 4: Relevance of GNbAC1 in multiple sclerosis treatment.
abstract: Multiple sclerosis associated retrovirus envelope protein (MSRV-Env) was repeatedly detected in brain lesions and blood of multiple sclerosis (MS) patients. We performed the first pharmacological characterisation of MSRV-Env on recombinant and native human TLR4. MSRV-Env is a full and highly potent TLR4 agonist of endogenous origin. MSRV-Env induces TLR4-dependent pro-inflammatory stimulation of immune cells in vitro and in vivo, and impairs oligodendrocytes precursor cells differentiation to myelinating oligodendrocytes. MSRV-Env may play a role in chronic inflammation and impaired remyelination in MS. GNbAC1, a selective monoclonal antibody, antagonizes MSRV-Env pathogenic effects and represents an innovative therapeutic approach of MS.
authors: GeNeuro Innovation SAS, Immeuble Forum 1, Archamps Technopole, 74160 Archamps, France.
authors: Alexandra
authors: A
authors: Madeira
authors: GeNeuro SA, 18 chemin des Aulx, 1228 Plan-Les-Ouates, Switzerland.
authors: Ingrid
authors: I
authors: Burgelin
authors: GeNeuro Innovation SAS, Immeuble Forum 1, Archamps Technopole, 74160 Archamps, France; GeNeuro SA, 18 chemin des Aulx, 1228 Plan-Les-Ouates, Switzerland.
authors: Hervé
authors: H
authors: Perron
authors: GeNeuro SA, 18 chemin des Aulx, 1228 Plan-Les-Ouates, Switzerland.
authors: Francois
authors: F
authors: Curtin
authors: GeNeuro SA, 18 chemin des Aulx, 1228 Plan-Les-Ouates, Switzerland.
authors: Alois B
authors: AB
authors: Lang
authors: GeNeuro Innovation SAS, Immeuble Forum 1, Archamps Technopole, 74160 Archamps, France. Electronic address: rf@geneuro.com.
authors: Raphael
authors: R
authors: Faucard
mesh_terms: D000818:Animals; D061067:Antibodies, Monoclonal, Humanized / Q000494:pharmacology*; D001921:Brain / Q000473:pathology; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism; D020077:Endogenous Retroviruses / Q000235:genetics; D005260:Female; D015686:Gene Products, env / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology; D018950:Lipopolysaccharide Receptors / Q000378:metabolism; D008070:Lipopolysaccharides / Q000009:adverse effects; D051379:Mice; D008810:Mice, Inbred C57BL; D009103:Multiple Sclerosis / Q000473:pathology*; D009836:Oligodendroglia / Q000187:drug effects; D015398:Signal Transduction / Q000187:drug effects; D013234:Stem Cells / Q000187:drug effects; D013997:Time Factors; D051197:Toll-Like Receptor 4 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D016207:Cytokines; D015686:Gene Products, env; D007166:Immunosuppressive Agents; D018950:Lipopolysaccharide Receptors; D008070:Lipopolysaccharides; C495345:TLR4 protein, human; D051197:Toll-Like Receptor 4; C581064:temelimab
keywords: GNbAC1; HERV-W; MSRV envelope; Monoclonal antibody; Multiple sclerosis; TLR4