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CNS Drugs

, Volume 33, Issue 11, pp 1133–1139 | Cite as

Treatment with Dimethyl Fumarate Enhances Cholinergic Transmission in Multiple Sclerosis

  • Carolina Gabri Nicoletti
  • Doriana Landi
  • Fabrizia Monteleone
  • Giorgia Mataluni
  • Maria Albanese
  • Benedetta Lauretti
  • Camilla Rocchi
  • Ilaria Simonelli
  • Laura Boffa
  • Fabio Buttari
  • Nicola Biagio Mercuri
  • Diego CentonzeEmail author
  • Girolama Alessandra Marfia
Original Research Article
  • 67 Downloads

Abstract

Background

Dimethyl fumarate (DMF) exerts anti-inflammatory effects in multiple sclerosis by activating the Nrf2 antioxidant pathway, which is also stimulated by acetylcholine via alpha-7 nicotinic acetylcholine receptors. In animal models, Nrf2 potentiates cholinergic synaptic plasticity.

Objective

The aim of this study was to test whether treatment with DMF modulates cholinergic pathways in relapsing-remitting multiple sclerosis (RRMS).

Methods

Patients starting DMF (20) or IFN-β 1a (20) and healthy subjects (20) were enrolled. Short-latency afferent inhibition (SAI), which is a transcranial stimulation measure of central cholinergic transmission, was recorded in patients and controls at baseline and, in patients only, after 6 months of treatment. Patients treated with DMF also underwent autonomic function testing to further explore peripheral and central cholinergic tone.

Results

At baseline, SAI was similar in patients and in controls (p = 0.983). Treatment with DMF significantly increased SAI (p = 0.01), while IFNβ had no effect (p = 0.80). In the cold face test, DMF treatment also increased reflex bradycardia (p = 0.013), and reduced diastolic blood pressure variation (p = 0.010), further indicating its ability to stimulate cholinergic transmission.

Conclusions

Treatment of MS patients with DMF results in increased cholinergic stimulation, with possible implications for neuroinflammation and neuroprotection.

Notes

Compliance with Ethical Standards

Conflict of interest

Carolina Gabri Nicoletti, Doriana Landi, Fabrizia Monteleone, Giorgia Mataluni, Maria Albanese, Benedetta Lauretti, Camilla Rocchi, Ilaria Simonelli, Laura Boffa, Fabio Buttari, Nicola Biagio Mercuri, Diego Centonze, and Girolama Alessandra Marfia declare that they have no conflict of interest.

Ethical approval

The study was approved by the local Ethics Committee of the University Hospital Tor Vergata, Rome (Italy).

Informed consent

All participants signed a written informed consent.

Funding

This study did not receive any financial support.

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Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  • Carolina Gabri Nicoletti
    • 1
  • Doriana Landi
    • 1
  • Fabrizia Monteleone
    • 1
  • Giorgia Mataluni
    • 1
  • Maria Albanese
    • 1
  • Benedetta Lauretti
    • 2
  • Camilla Rocchi
    • 2
  • Ilaria Simonelli
    • 1
    • 4
  • Laura Boffa
    • 1
  • Fabio Buttari
    • 3
  • Nicola Biagio Mercuri
    • 2
    • 5
  • Diego Centonze
    • 1
    • 3
    Email author
  • Girolama Alessandra Marfia
    • 1
    • 3
  1. 1.Multiple Sclerosis Clinical and Research Unit, Department of Systems MedicineTor Vergata University and HospitalRomeItaly
  2. 2.Neurology Unit, Department of Systems MedicineTor Vergata University and HospitalRomeItaly
  3. 3.Neurology and Neurorehabilitation UnitsIRCCS NEUROMEDPozzilliItaly
  4. 4.Service of Medical Statistics and Information TechnologyFondazione Fatebenefratelli per la Ricerca e la Formazione Sanitaria e SocialeRomeItaly
  5. 5.Laboratory of Experimental NeurologyIRCCS Fondazione Santa LuciaRomeItaly

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