A Minimally-invasive Blood-derived Biomarker of Oligodendrocyte Cell-loss in Multiple Sclerosis

EBioMedicine. 2016 Aug;10:227-35. doi: 10.1016/j.ebiom.2016.06.031. Epub 2016 Jun 27.

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.

Keywords: Biomarker discovery; Circulating free DNA; Cuprizone; Human patients; Oligodendrocyte; Relapsing-remitting multiple sclerosis.

MeSH terms

  • Adult
  • Animals
  • Biomarkers*
  • Cell Line
  • Central Nervous System / metabolism
  • Central Nervous System / pathology
  • DNA Methylation
  • Female
  • Humans
  • Mice
  • Multiple Sclerosis / blood*
  • Multiple Sclerosis / diagnosis*
  • Multiple Sclerosis / genetics
  • Multiple Sclerosis, Relapsing-Remitting / blood
  • Multiple Sclerosis, Relapsing-Remitting / diagnosis
  • Multiple Sclerosis, Relapsing-Remitting / genetics
  • Myelin-Oligodendrocyte Glycoprotein / genetics
  • Oligodendroglia / metabolism
  • Oligodendroglia / pathology*
  • Schwann Cells / metabolism

Substances

  • Biomarkers
  • Myelin-Oligodendrocyte Glycoprotein