Treatment Against Human Endogenous Retrovirus: A Possible Personalized Medicine Approach for Multiple Sclerosis
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 lesion...
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| Veröffentlicht in: | Molecular diagnosis & therapy 2015-10, Vol.19 (5), p.255-265 |
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| description | 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. |
| doi_str_mv | 10.1007/s40291-015-0166-z |
| format | Article |
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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.</description><identifier>ISSN: 1177-1062</identifier><identifier>EISSN: 1179-2000</identifier><identifier>DOI: 10.1007/s40291-015-0166-z</identifier><identifier>PMID: 26376649</identifier><language>eng</language><publisher>Cham: Springer International Publishing</publisher><subject>Animals ; Antibodies, Monoclonal, Humanized - pharmacology ; Antibodies, Monoclonal, Humanized - therapeutic use ; Biomarkers ; Biomedical and Life Sciences ; Biomedicine ; Cancer Research ; Clinical Trials, Phase II as Topic ; Cytokines ; Disease ; Disease Models, Animal ; Drugs ; Endogenous Retroviruses - drug effects ; Endogenous Retroviruses - genetics ; Endogenous Retroviruses - metabolism ; Gene Products, env - antagonists & inhibitors ; Gene Products, env - blood ; Gene Products, env - cerebrospinal fluid ; Gene Products, env - genetics ; Human endogenous retrovirus ; Human Genetics ; Humans ; Laboratory Medicine ; Lymphocytes ; Mice ; Molecular Medicine ; Multiple sclerosis ; Multiple Sclerosis - drug therapy ; Multiple Sclerosis - virology ; Neurodegeneration ; Pathology ; Pharmacotherapy ; Precision Medicine ; Proteins ; Review Article ; RNA, Viral - blood ; RNA, Viral - cerebrospinal fluid ; RNA, Viral - drug effects ; Studies</subject><ispartof>Molecular diagnosis & therapy, 2015-10, Vol.19 (5), p.255-265</ispartof><rights>Springer International Publishing Switzerland 2015</rights><rights>Copyright Springer Science & Business Media Oct 2015</rights><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c475t-8f0cae12a829bb3fdbd42aa07a748336a898b2dee8b7f64d7347fbc684a76cac3</citedby><cites>FETCH-LOGICAL-c475t-8f0cae12a829bb3fdbd42aa07a748336a898b2dee8b7f64d7347fbc684a76cac3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1007/s40291-015-0166-z$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1007/s40291-015-0166-z$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>314,778,782,27907,27908,41471,42540,51302</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/26376649$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Curtin, François</creatorcontrib><creatorcontrib>Perron, Hervé</creatorcontrib><creatorcontrib>Faucard, Raphael</creatorcontrib><creatorcontrib>Porchet, Hervé</creatorcontrib><creatorcontrib>Lang, Alois B.</creatorcontrib><title>Treatment Against Human Endogenous Retrovirus: A Possible Personalized Medicine Approach for Multiple Sclerosis</title><title>Molecular diagnosis & therapy</title><addtitle>Mol Diagn Ther</addtitle><addtitle>Mol Diagn Ther</addtitle><description>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. 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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.</abstract><cop>Cham</cop><pub>Springer International Publishing</pub><pmid>26376649</pmid><doi>10.1007/s40291-015-0166-z</doi><tpages>11</tpages></addata></record> |
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| subjects | Animals Antibodies, Monoclonal, Humanized - pharmacology Antibodies, Monoclonal, Humanized - therapeutic use Biomarkers Biomedical and Life Sciences Biomedicine Cancer Research Clinical Trials, Phase II as Topic Cytokines Disease Disease Models, Animal Drugs Endogenous Retroviruses - drug effects Endogenous Retroviruses - genetics Endogenous Retroviruses - metabolism Gene Products, env - antagonists & inhibitors Gene Products, env - blood Gene Products, env - cerebrospinal fluid Gene Products, env - genetics Human endogenous retrovirus Human Genetics Humans Laboratory Medicine Lymphocytes Mice Molecular Medicine Multiple sclerosis Multiple Sclerosis - drug therapy Multiple Sclerosis - virology Neurodegeneration Pathology Pharmacotherapy Precision Medicine Proteins Review Article RNA, Viral - blood RNA, Viral - cerebrospinal fluid RNA, Viral - drug effects Studies |
| title | Treatment Against Human Endogenous Retrovirus: A Possible Personalized Medicine Approach for Multiple Sclerosis |
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