Contributions
Abstract: EP1622
Type: Poster Sessions
Abstract Category: Therapy - Neuroprotection and Repair
Introduction: Dimethyl fumarate (DMF) exerts antinflammatory effects in multiple sclerosis (MS) 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 transmission. Increased cholinergic tone has been associated with better prognosis in MS. Central cholinergic functioning can be tested non-invasively in humans by Short-latency Afferent Inhibition (SAI), a paired-pulse transcranial magnetic stimulation (TMS) protocol in which motor evoked potentials are conditioned by peripheral nerve electrical stimulus delivered before magnetic stimulation of motor cortex.
Aim of the study: To test whether treatment with DMF modulates cholinergic pathways in relapsing-remitting multiple sclerosis (RRMS) compared to Interferon-β 1a (INF-β 1a).
Methods: Patients starting DMF (20; DMFG) or INF-β 1a (20; INFG) and healthy subjects (20; HSG) were enrolled. SAI 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 INF-β 1a had no effect (p=0.80). At 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.
Conclusion: DMF treatment of MS patients is associated with changes of central and autonomic cholinergic tone. Increased SAI was founded in DMF treated patients, but not in INF-βG, confirming the specificity of DMF effect. This may represent a novel mechanism of action accounting for DMF efficacy in RRMS, with possible implications for neuroinflammation and neuroprotection. Future studies are needed to confirm these data and to explore the potential effect of DMF in restoring normal cholinergic transmission in cognitively impaired MS patients.
Disclosure: Dr. Albanese received honoraria for traveling from Almirall, Biogen, Merck Serono, Novartis,and Teva. She is involved as sub-investigator in clinical trials for Bayer Schering, Biogen Idec, Novartis, Merck Serono, Sanofi-Genzyme, Teva, Roche.
Dr. Boffa received travel funding from Almirall, Merck Serono, Sanofi-Genzyme and Teva.
Dr. Buttari acted as Advisory Board member of Teva.
Dr. Centonze is an Advisory Board member of Almirall, Bayer Schering, Biogen, GW Pharmaceuticals, Merck Serono, Novartis, Roche, Sanofi-Genzyme, Teva and received honoraria for speaking or consultation fees from Almirall, Bayer Schering, Biogen, GW Pharmaceuticals, Merck Serono, Novartis, Roche, Sanofi-Genzyme, Teva. He is also the principal investigator in clinical trials for Bayer Schering, Biogen, Merck Serono, Mitsubishi, Novartis, Roche, Sanofi-Genzyme, Teva. His preclinical and clinical research was supported by grants from Bayer Schering, Biogen Idec, Celgene, Merck Serono, Novartis, Roche, Sanofi- Genzyme e Teva.
Dr. Landi received travel funding from Biogen, Merck Serono, Sanofi-Genzyme and Teva, honoraria for speaking from Sanofi-Genzyme and Teva, and consultation fees from Merck Serono and Teva. She is subinvestigator in clinical trials being conducted for Biogen, Merck Serono, Novartis, Roche and Teva.
Dr. Lauretti has nothing to declare.
Dr. Marfia is an Advisory Board member of Biogen Idec, Genzyme, Merck-Serono, Novartis, Teva and received honoraria for speaking or consultation fees from Almirall, Bayer Schering, Biogen Idec, Merck Serono, Novartis, Sanofi-Genzyme, Teva. She is the principal investigator in clinical trials for Actelion, Biogen Idec, Merck Serono, Mitsubishi, Novartis, Roche, Sanofi-Genzyme, Teva.
Dr. Mataluni received travel funding from Almirall, Biogen, Novartis and Sanofi-Genzyme; honoraria for speaking from Biogen. She is subinvestigator in clinical trials being conducted for Biogen, Merck Serono, Novartis, Roche and Teva.
Dr. Mercuri has nothing to declare.
Dr. Monteleone received funding for traveling from Almirall, Biogen and Sanofi-Genzyme and consultation fees from Almirall.
Dr. Nicoletti received funding for traveling from Almirall, Biogen, Merck and Sanofi-Genzyme.
Dr. Rocchi has nothing to declare.
Dr. Simonelli has nothing to declare.
Abstract: EP1622
Type: Poster Sessions
Abstract Category: Therapy - Neuroprotection and Repair
Introduction: Dimethyl fumarate (DMF) exerts antinflammatory effects in multiple sclerosis (MS) 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 transmission. Increased cholinergic tone has been associated with better prognosis in MS. Central cholinergic functioning can be tested non-invasively in humans by Short-latency Afferent Inhibition (SAI), a paired-pulse transcranial magnetic stimulation (TMS) protocol in which motor evoked potentials are conditioned by peripheral nerve electrical stimulus delivered before magnetic stimulation of motor cortex.
Aim of the study: To test whether treatment with DMF modulates cholinergic pathways in relapsing-remitting multiple sclerosis (RRMS) compared to Interferon-β 1a (INF-β 1a).
Methods: Patients starting DMF (20; DMFG) or INF-β 1a (20; INFG) and healthy subjects (20; HSG) were enrolled. SAI 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 INF-β 1a had no effect (p=0.80). At 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.
Conclusion: DMF treatment of MS patients is associated with changes of central and autonomic cholinergic tone. Increased SAI was founded in DMF treated patients, but not in INF-βG, confirming the specificity of DMF effect. This may represent a novel mechanism of action accounting for DMF efficacy in RRMS, with possible implications for neuroinflammation and neuroprotection. Future studies are needed to confirm these data and to explore the potential effect of DMF in restoring normal cholinergic transmission in cognitively impaired MS patients.
Disclosure: Dr. Albanese received honoraria for traveling from Almirall, Biogen, Merck Serono, Novartis,and Teva. She is involved as sub-investigator in clinical trials for Bayer Schering, Biogen Idec, Novartis, Merck Serono, Sanofi-Genzyme, Teva, Roche.
Dr. Boffa received travel funding from Almirall, Merck Serono, Sanofi-Genzyme and Teva.
Dr. Buttari acted as Advisory Board member of Teva.
Dr. Centonze is an Advisory Board member of Almirall, Bayer Schering, Biogen, GW Pharmaceuticals, Merck Serono, Novartis, Roche, Sanofi-Genzyme, Teva and received honoraria for speaking or consultation fees from Almirall, Bayer Schering, Biogen, GW Pharmaceuticals, Merck Serono, Novartis, Roche, Sanofi-Genzyme, Teva. He is also the principal investigator in clinical trials for Bayer Schering, Biogen, Merck Serono, Mitsubishi, Novartis, Roche, Sanofi-Genzyme, Teva. His preclinical and clinical research was supported by grants from Bayer Schering, Biogen Idec, Celgene, Merck Serono, Novartis, Roche, Sanofi- Genzyme e Teva.
Dr. Landi received travel funding from Biogen, Merck Serono, Sanofi-Genzyme and Teva, honoraria for speaking from Sanofi-Genzyme and Teva, and consultation fees from Merck Serono and Teva. She is subinvestigator in clinical trials being conducted for Biogen, Merck Serono, Novartis, Roche and Teva.
Dr. Lauretti has nothing to declare.
Dr. Marfia is an Advisory Board member of Biogen Idec, Genzyme, Merck-Serono, Novartis, Teva and received honoraria for speaking or consultation fees from Almirall, Bayer Schering, Biogen Idec, Merck Serono, Novartis, Sanofi-Genzyme, Teva. She is the principal investigator in clinical trials for Actelion, Biogen Idec, Merck Serono, Mitsubishi, Novartis, Roche, Sanofi-Genzyme, Teva.
Dr. Mataluni received travel funding from Almirall, Biogen, Novartis and Sanofi-Genzyme; honoraria for speaking from Biogen. She is subinvestigator in clinical trials being conducted for Biogen, Merck Serono, Novartis, Roche and Teva.
Dr. Mercuri has nothing to declare.
Dr. Monteleone received funding for traveling from Almirall, Biogen and Sanofi-Genzyme and consultation fees from Almirall.
Dr. Nicoletti received funding for traveling from Almirall, Biogen, Merck and Sanofi-Genzyme.
Dr. Rocchi has nothing to declare.
Dr. Simonelli has nothing to declare.