title: A Minimally-invasive Blood-derived Biomarker of Oligodendrocyte Cell-loss in Multiple Sclerosis.
abstract: 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.
authors.affiliation: Research Institute, Islet Biology, Winthrop-University Hospital, Mineola, NY, USA.
authors.forename: John A
authors.initials: JA
authors.lastname: Olsen
authors.affiliation: Research Institute, Islet Biology, Winthrop-University Hospital, Mineola, NY, USA.
authors.forename: Lauren A
authors.initials: LA
authors.lastname: Kenna
authors.affiliation: Research Institute, Islet Biology, Winthrop-University Hospital, Mineola, NY, USA.
authors.forename: Regine C
authors.initials: RC
authors.lastname: Tipon
authors.affiliation: Research Institute, Islet Biology, Winthrop-University Hospital, Mineola, NY, USA.
authors.forename: Michael G
authors.initials: MG
authors.lastname: Spelios
authors.affiliation: Department of Neuroscience, Winthrop-University Hospital Mineola, NY, USA.
authors.forename: Mark M
authors.initials: MM
authors.lastname: Stecker
authors.affiliation: Research Institute, Islet Biology, Winthrop-University Hospital, Mineola, NY, USA; Stony Brook University School of Medicine, Stony Brook, NY, USA. Electronic address: eakirav@winthrop.org.
authors.forename: Eitan M
authors.initials: EM
authors.lastname: Akirav
mesh_terms: D000328:Adult; D000818:Animals; D015415:Biomarkers; D002460:Cell Line; D002490:Central Nervous System / Q000378:metabolism / Q000473:pathology; D019175:DNA Methylation; D005260:Female; D006801:Humans; D051379:Mice; D009103:Multiple Sclerosis / Q000097:blood* / Q000175:diagnosis* / Q000235:genetics; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000097:blood / Q000175:diagnosis / Q000235:genetics; D063308:Myelin-Oligodendrocyte Glycoprotein / Q000235:genetics; D009836:Oligodendroglia / Q000378:metabolism / Q000473:pathology*; D012583:Schwann Cells / Q000378:metabolism
chemical_list: D015415:Biomarkers; D063308:Myelin-Oligodendrocyte Glycoprotein
keywords: Biomarker discovery; Circulating free DNA; Cuprizone; Human patients; Oligodendrocyte; Relapsing-remitting multiple sclerosis