A Minimally-invasive Blood-derived Biomarker of Oligodendrocyte Cell-loss in Multiple Sclerosis
Multiple sclerosis (MS) is a neurodegenerative disease of the central nervous system (CNS). Minimally invasive biomarkers of MS are required for disease diagnosis and treatment. Differentially methylated circulating-free DNA (cfDNA) is a useful biomarker for disease diagnosis and prognosis, and may...
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| Format: | Article |
| Language: | English |
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Elsevier
2016-08-01
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| Series: | EBioMedicine |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2352396416302882 |
| _version_ | 1819050330228260864 |
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| author | John A. Olsen Lauren A. Kenna Regine C. Tipon Michael G. Spelios Mark M. Stecker Eitan M. Akirav |
| author_facet | John A. Olsen Lauren A. Kenna Regine C. Tipon Michael G. Spelios Mark M. Stecker Eitan M. Akirav |
| author_sort | John A. Olsen |
| collection | DOAJ |
| description | Multiple sclerosis (MS) is a neurodegenerative disease of the central nervous system (CNS). Minimally invasive biomarkers of MS are required for disease diagnosis and treatment. Differentially methylated circulating-free DNA (cfDNA) is a useful biomarker for disease diagnosis and prognosis, and may offer to be a viable approach for understanding MS. Here, methylation-specific primers and quantitative real-time PCR were used to study methylation patterns of the myelin oligodendrocyte glycoprotein (MOG) gene, which is expressed primarily in myelin-producing oligodendrocytes (ODCs). MOG-DNA was demethylated in O4+ ODCs in mice and in DNA from human oligodendrocyte precursor cells (OPCs) when compared with other cell types. In the cuprizone-fed mouse model of demyelination, ODC derived demethylated MOG cfDNA was increased in serum and was associated with tissue-wide demyelination, demonstrating the utility of demethylated MOG cfDNA as a biomarker of ODC death. Collected sera from patients with active (symptomatic) relapsing-remitting MS (RRMS) demonstrated a higher signature of demethylated MOG cfDNA when compared with patients with inactive disease and healthy controls. Taken together, these results offer a minimally invasive approach to measuring ODC death in the blood of MS patients that may be used to monitor disease progression. |
| first_indexed | 2024-12-21T11:46:20Z |
| format | Article |
| id | doaj.art-2f52b81ca96c44a088633b9229625d60 |
| institution | Directory Open Access Journal |
| issn | 2352-3964 |
| language | English |
| last_indexed | 2024-12-21T11:46:20Z |
| publishDate | 2016-08-01 |
| publisher | Elsevier |
| record_format | Article |
| series | EBioMedicine |
| spelling | doaj.art-2f52b81ca96c44a088633b9229625d602022-12-21T19:05:10ZengElsevierEBioMedicine2352-39642016-08-0110C22723510.1016/j.ebiom.2016.06.031A Minimally-invasive Blood-derived Biomarker of Oligodendrocyte Cell-loss in Multiple SclerosisJohn A. Olsen0Lauren A. Kenna1Regine C. Tipon2Michael G. Spelios3Mark M. Stecker4Eitan M. Akirav5Research Institute, Islet Biology, Winthrop-University Hospital, Mineola, NY, USAResearch Institute, Islet Biology, Winthrop-University Hospital, Mineola, NY, USAResearch Institute, Islet Biology, Winthrop-University Hospital, Mineola, NY, USAResearch Institute, Islet Biology, Winthrop-University Hospital, Mineola, NY, USADepartment of Neuroscience, Winthrop-University Hospital Mineola, NY, USAResearch Institute, Islet Biology, Winthrop-University Hospital, Mineola, NY, USAMultiple sclerosis (MS) is a neurodegenerative disease of the central nervous system (CNS). Minimally invasive biomarkers of MS are required for disease diagnosis and treatment. Differentially methylated circulating-free DNA (cfDNA) is a useful biomarker for disease diagnosis and prognosis, and may offer to be a viable approach for understanding MS. Here, methylation-specific primers and quantitative real-time PCR were used to study methylation patterns of the myelin oligodendrocyte glycoprotein (MOG) gene, which is expressed primarily in myelin-producing oligodendrocytes (ODCs). MOG-DNA was demethylated in O4+ ODCs in mice and in DNA from human oligodendrocyte precursor cells (OPCs) when compared with other cell types. In the cuprizone-fed mouse model of demyelination, ODC derived demethylated MOG cfDNA was increased in serum and was associated with tissue-wide demyelination, demonstrating the utility of demethylated MOG cfDNA as a biomarker of ODC death. Collected sera from patients with active (symptomatic) relapsing-remitting MS (RRMS) demonstrated a higher signature of demethylated MOG cfDNA when compared with patients with inactive disease and healthy controls. Taken together, these results offer a minimally invasive approach to measuring ODC death in the blood of MS patients that may be used to monitor disease progression.http://www.sciencedirect.com/science/article/pii/S2352396416302882Relapsing-remitting multiple sclerosisOligodendrocyteCuprizoneHuman patientsCirculating free DNABiomarker discovery |
| spellingShingle | John A. Olsen Lauren A. Kenna Regine C. Tipon Michael G. Spelios Mark M. Stecker Eitan M. Akirav A Minimally-invasive Blood-derived Biomarker of Oligodendrocyte Cell-loss in Multiple Sclerosis EBioMedicine Relapsing-remitting multiple sclerosis Oligodendrocyte Cuprizone Human patients Circulating free DNA Biomarker discovery |
| title | A Minimally-invasive Blood-derived Biomarker of Oligodendrocyte Cell-loss in Multiple Sclerosis |
| title_full | A Minimally-invasive Blood-derived Biomarker of Oligodendrocyte Cell-loss in Multiple Sclerosis |
| title_fullStr | A Minimally-invasive Blood-derived Biomarker of Oligodendrocyte Cell-loss in Multiple Sclerosis |
| title_full_unstemmed | A Minimally-invasive Blood-derived Biomarker of Oligodendrocyte Cell-loss in Multiple Sclerosis |
| title_short | A Minimally-invasive Blood-derived Biomarker of Oligodendrocyte Cell-loss in Multiple Sclerosis |
| title_sort | minimally invasive blood derived biomarker of oligodendrocyte cell loss in multiple sclerosis |
| topic | Relapsing-remitting multiple sclerosis Oligodendrocyte Cuprizone Human patients Circulating free DNA Biomarker discovery |
| url | http://www.sciencedirect.com/science/article/pii/S2352396416302882 |
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