title: Cerebrospinal fluid mtDNA concentration is elevated in multiple sclerosis disease and responds to treatment.
abstract: Mitochondrial dysfunction is increasingly recognized as an important feature of multiple sclerosis (MS) pathology and may be relevant for clinical disease progression. However, it is unknown whether mitochondrial DNA (mtDNA) levels in the cerebrospinal fluid (CSF) associate with disease progression and therapeutic response.
  
  
  
  To evaluate whether CSF concentrations of mtDNA in MS patients can serve as a marker of ongoing neuropathology and may be helpful to differentiate between MS disease subtypes. To explore the effect of disease-modifying therapies on mtDNA levels in the CSF.
  
  
  
  CSF mtDNA was measured using a digital polymerase chain reaction (PCR) CSF mtDNA in two independent MS cohorts. The cohorts included 92 relapsing-remitting multiple sclerosis (RRMS) patients, 40 progressive multiple sclerosis (PMS) patients (27 secondary progressive and 13 primary progressive), 50 various neurologic disease controls, and 5 healthy controls.
  
  
  
  Patients with PMS showed a significant increase in CSF mtDNA compared to non-inflammatory neurologic disease controls. Patients with higher T2 lesion volumes and lower normalized brain volumes showed increased concentration of mtDNA. Patients treated with fingolimod had significantly lower mtDNA copy levels at follow-up compared to baseline.
  
  
  
  Our results showed a non-specific elevation of concentration of mtDNA in PMS patients. mtDNA concentrations respond to fingolimod and may be used to monitor biological effect of this treatment.
authors.affiliation: Department of Neurology, MS Center Amsterdam, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Cyra E
authors.initials: CE
authors.lastname: Leurs
authors.affiliation: Institute of Biomedical Research of Barcelona, CSIC-IDIBAPS, CIBERNED, Barcelona, Spain.
authors.forename: Petar
authors.initials: P
authors.lastname: Podlesniy
authors.affiliation: Institute of Biomedical Research of Barcelona, CSIC-IDIBAPS, CIBERNED, Barcelona, Spain.
authors.forename: Ramon
authors.initials: R
authors.lastname: Trullas
authors.affiliation: Department of Neurology, MS Center Amsterdam, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Lisanne
authors.initials: L
authors.lastname: Balk
authors.affiliation: Departments of Radiology and Nuclear Medicine, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Martijn D
authors.initials: MD
authors.lastname: Steenwijk
authors.affiliation: Neurochemistry Laboratory and Biobank, Department of Clinical Chemistry, Neuroscience Campus Amsterdam, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Arjan
authors.initials: A
authors.lastname: Malekzadeh
authors.affiliation: Neuroimmunology Unit, Department of Clinical Neuroscience, Karolinska Institutet and Karolinska University Hospital, Stockholm, Sweden.
authors.forename: Fredrik
authors.initials: F
authors.lastname: Piehl
authors.affiliation: Department of Neurology, MS Center Amsterdam, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Bernard Mj
authors.initials: BM
authors.lastname: Uitdehaag
authors.affiliation: Department of Neurology, MS Center Amsterdam, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Joep
authors.initials: J
authors.lastname: Killestein
authors.affiliation: Department of Molecular Cell Biology and Immunology, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Jack
authors.initials: J
authors.lastname: van Horssen
authors.affiliation: Neurochemistry Laboratory and Biobank, Department of Clinical Chemistry, Neuroscience Campus Amsterdam, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: C E
authors.initials: CE
authors.lastname: Teunissen
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000134:cerebrospinal fluid*; D004272:DNA, Mitochondrial / Q000134:cerebrospinal fluid*; D018450:Disease Progression; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D008928:Mitochondria / Q000378:metabolism*; D009103:Multiple Sclerosis / Q000134:cerebrospinal fluid / Q000188:drug therapy* / Q000473:pathology; D020528:Multiple Sclerosis, Chronic Progressive / Q000134:cerebrospinal fluid; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000134:cerebrospinal fluid
chemical_list: D015415:Biomarkers; D004272:DNA, Mitochondrial
keywords: Multiple sclerosis; biomarkers; cerebrospinal fluid; digital PCR; mitochondrial DNA