Cerebrospinal fluid mtDNA concentration is elevated in multiple sclerosis disease and responds to treatment

Cyra E Leurs, Petar Podlesniy, Ramon Trullas, Lisanne Balk, Martijn D Steenwijk, Arjan Malekzadeh, Fredrik Piehl, Bernard Mj Uitdehaag, Joep Killestein, Jack van Horssen, C E Teunissen

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

BACKGROUND: 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.

OBJECTIVES: 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.

METHODS: 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.

RESULTS: 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.

CONCLUSION: 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.

Original languageEnglish
Pages (from-to)472-480
Number of pages9
JournalMultiple Sclerosis
Volume24
Issue number4
Early online date1 Mar 2017
DOIs
Publication statusPublished - 1 Apr 2018

Cite this

@article{a126f620a92140e78154024e170f941e,
title = "Cerebrospinal fluid mtDNA concentration is elevated in multiple sclerosis disease and responds to treatment",
abstract = "BACKGROUND: 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.OBJECTIVES: 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.METHODS: 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.RESULTS: 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.CONCLUSION: 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.",
keywords = "Journal Article",
author = "Leurs, {Cyra E} and Petar Podlesniy and Ramon Trullas and Lisanne Balk and Steenwijk, {Martijn D} and Arjan Malekzadeh and Fredrik Piehl and Uitdehaag, {Bernard Mj} and Joep Killestein and {van Horssen}, Jack and Teunissen, {C E}",
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Cerebrospinal fluid mtDNA concentration is elevated in multiple sclerosis disease and responds to treatment. / Leurs, Cyra E; Podlesniy, Petar; Trullas, Ramon; Balk, Lisanne; Steenwijk, Martijn D; Malekzadeh, Arjan; Piehl, Fredrik; Uitdehaag, Bernard Mj; Killestein, Joep; van Horssen, Jack; Teunissen, C E.

In: Multiple Sclerosis, Vol. 24, No. 4, 01.04.2018, p. 472-480.

Research output: Contribution to journalArticleAcademicpeer-review

TY - JOUR

T1 - Cerebrospinal fluid mtDNA concentration is elevated in multiple sclerosis disease and responds to treatment

AU - Leurs, Cyra E

AU - Podlesniy, Petar

AU - Trullas, Ramon

AU - Balk, Lisanne

AU - Steenwijk, Martijn D

AU - Malekzadeh, Arjan

AU - Piehl, Fredrik

AU - Uitdehaag, Bernard Mj

AU - Killestein, Joep

AU - van Horssen, Jack

AU - Teunissen, C E

PY - 2018/4/1

Y1 - 2018/4/1

N2 - BACKGROUND: 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.OBJECTIVES: 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.METHODS: 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.RESULTS: 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.CONCLUSION: 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.

AB - BACKGROUND: 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.OBJECTIVES: 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.METHODS: 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.RESULTS: 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.CONCLUSION: 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.

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DO - 10.1177/1352458517699874

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VL - 24

SP - 472

EP - 480

JO - Multiple Sclerosis

JF - Multiple Sclerosis

SN - 1352-4585

IS - 4

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