title: Treatment against human endogenous retrovirus: a possible personalized medicine approach for multiple sclerosis.
abstract: Human endogenous retroviruses (HERV) represent about 8 % of the human genome. Some of these genetic elements are expressed in pathological circumstances. A HERV protein, the multiple sclerosis-associated retrovirus (MSRV) envelope protein (MSRV-Env), is expressed in the blood and active brain lesions of multiple sclerosis (MS) patients. It possesses pro-inflammatory and myelinotoxic properties. The patterns of expression and pathogenic properties of MSRV-Env make it a relevant drug target for MS therapeutics-in particular for preventing neurodegeneration, a key component of progressive forms of MS. An immunoglobulin G4 monoclonal antibody (mAb), called GNbAC1, has been developed to neutralize this pathogenic target. After showing neutralizing effects in vitro and in mouse models of MS, GNbAC1 is now in phase II clinical development. MSRV-related biomarkers such as MSRV-Env and MSRV polymerase (MSRV-Pol) gene transcripts are overexpressed in the blood and cerebrospinal fluid of patients with MS. These biomarkers may have prognostic value for long-term MS evolution, and their transcription levels in blood decline during treatments with GNbAC1, which has also been reported in patients administered reference MS drugs such as natalizumab or interferon-β. GNbAC1 as a new MSRV-Env-antagonist mAb could be a specific and causal treatment for MS, with a particular application for progressive forms of the disease. For possible use in companion diagnostic tests, MSRV-associated biomarkers could open the door to a personalized therapeutic approach for MS.
authors.affiliation: GeNeuro SA, 18 Chemin des Aulx, Plan-les-Ouates, 1228, Geneva, Switzerland. fc@geneuro.com.|Division of Clinical Pharmacology and Toxicology Division, Geneva University Hospital, Geneva, Switzerland. fc@geneuro.com.
authors.forename: François
authors.initials: F
authors.lastname: Curtin
authors.affiliation: GeNeuro SA, 18 Chemin des Aulx, Plan-les-Ouates, 1228, Geneva, Switzerland.
authors.forename: Hervé
authors.initials: H
authors.lastname: Perron
authors.affiliation: GeNeuro SA, 18 Chemin des Aulx, Plan-les-Ouates, 1228, Geneva, Switzerland.
authors.forename: Raphael
authors.initials: R
authors.lastname: Faucard
authors.affiliation: GeNeuro SA, 18 Chemin des Aulx, Plan-les-Ouates, 1228, Geneva, Switzerland.|Department of Pharmacology, Faculty of Health Sciences, University of Pretoria, Pretoria, South Africa.
authors.forename: Hervé
authors.initials: H
authors.lastname: Porchet
authors.affiliation: GeNeuro SA, 18 Chemin des Aulx, Plan-les-Ouates, 1228, Geneva, Switzerland.
authors.forename: Alois B
authors.initials: AB
authors.lastname: Lang
mesh_terms: D000818:Animals; D061067:Antibodies, Monoclonal, Humanized / Q000494:pharmacology* / Q000627:therapeutic use; D017322:Clinical Trials, Phase II as Topic; D004195:Disease Models, Animal; D020077:Endogenous Retroviruses / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D015686:Gene Products, env / Q000037:antagonists & inhibitors* / Q000097:blood / Q000134:cerebrospinal fluid / Q000235:genetics; D006801:Humans; D051379:Mice; D009103:Multiple Sclerosis / Q000188:drug therapy* / Q000821:virology; D057285:Precision Medicine; D012367:RNA, Viral / Q000097:blood / Q000134:cerebrospinal fluid / Q000187:drug effects
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D015686:Gene Products, env; D012367:RNA, Viral; C581064:temelimab