title: Impact of glatiramer acetate on paraclinical markers of neuroprotection in multiple sclerosis: A prospective observational clinical trial.
abstract: Data from in vitro and animal studies support a neuroprotective role of glatiramer acetate (GA) in multiple sclerosis (MS). We investigated prospectively whether treatment with GA leads to clinical and paraclinical changes associated with neuroprotection in patients with relapsing-remitting (RR) MS. Primary aim of this clinical study was to determine serum BDNF levels in RR-MS patients who were started on GA as compared to patients who remained therapy-naive throughout 24 months. Secondary outcomes included relapses and EDSS, cognition, quality of life, fatigue and depression, BDNF expression levels on peripheral immune cells (FACS, RT-PCR), serum anti-myelin basic peptide (MBP) antibody status, evoked potential and cerebral MRI studies. While GA treatment did not alter serum levels or expression levels on peripheral immune cells of BDNF over time it resulted in a transient increase of serum IgG antibody response to MBP, mainly due to subtype IgG1 (p<0.05), after 3 months. However, no significant differences were found between GA treated and therapy-naive patients with regard to serum BDNF and intracellular BDNF expression levels, nerve conduction (including median and tibial nerve somatosensory, pattern-shift visual and upper and lower limb motor evoked potentials) or MRI (including volume of hyperintense lesions, volume of hypointense lesions after CE, mean diffusivity and fractional anisotropy) outcome parameters. In conclusion, our findings do not support a major impact of GA treatment on paraclinical markers of neuroprotection in human RR-MS.
authors.affiliation: Clinical Department of Neurology, Medical University of Innsbruck, Anichstrasse 35, 6020 Innsbruck, Austria; Clinics for Neurological Rehabilitation Münster, Groeben 700, 6232 Münster, Austria; Department of Radiology, Medical University Innsbruck, Anichstrasse 35, 6020 Innsbruck, Austria. Electronic address: rainer.ehling@i-med.ac.at.
authors.forename: Rainer
authors.initials: R
authors.lastname: Ehling
authors.affiliation: Clinical Department of Neurology, Medical University of Innsbruck, Anichstrasse 35, 6020 Innsbruck, Austria; Clinics for Neurological Rehabilitation Münster, Groeben 700, 6232 Münster, Austria; Department of Radiology, Medical University Innsbruck, Anichstrasse 35, 6020 Innsbruck, Austria. Electronic address: franziska.dipauli@i-med.ac.at.
authors.forename: Franziska
authors.initials: F
authors.lastname: Di Pauli
authors.affiliation: Clinical Department of Neurology, Medical University of Innsbruck, Anichstrasse 35, 6020 Innsbruck, Austria; Clinics for Neurological Rehabilitation Münster, Groeben 700, 6232 Münster, Austria; Department of Radiology, Medical University Innsbruck, Anichstrasse 35, 6020 Innsbruck, Austria. Electronic address: peter.lackner@i-med.ac.at.
authors.forename: Peter
authors.initials: P
authors.lastname: Lackner
authors.affiliation: Clinical Department of Neurology, Medical University of Innsbruck, Anichstrasse 35, 6020 Innsbruck, Austria; Clinics for Neurological Rehabilitation Münster, Groeben 700, 6232 Münster, Austria; Department of Radiology, Medical University Innsbruck, Anichstrasse 35, 6020 Innsbruck, Austria. Electronic address: carolyn.rainer@liverpool.ac.uk.
authors.forename: Carolyn
authors.initials: C
authors.lastname: Rainer
authors.affiliation: Clinical Department of Neurology, Medical University of Innsbruck, Anichstrasse 35, 6020 Innsbruck, Austria; Clinics for Neurological Rehabilitation Münster, Groeben 700, 6232 Münster, Austria; Department of Radiology, Medical University Innsbruck, Anichstrasse 35, 6020 Innsbruck, Austria. Electronic address: viktoria.kraus@tirolkliniken.at.
authors.forename: Viktoria
authors.initials: V
authors.lastname: Kraus
authors.affiliation: Clinical Department of Neurology, Medical University of Innsbruck, Anichstrasse 35, 6020 Innsbruck, Austria; Clinics for Neurological Rehabilitation Münster, Groeben 700, 6232 Münster, Austria; Department of Radiology, Medical University Innsbruck, Anichstrasse 35, 6020 Innsbruck, Austria. Electronic address: harald.hegen@i-med.ac.at.
authors.forename: Harald
authors.initials: H
authors.lastname: Hegen
authors.affiliation: Clinical Department of Neurology, Medical University of Innsbruck, Anichstrasse 35, 6020 Innsbruck, Austria; Clinics for Neurological Rehabilitation Münster, Groeben 700, 6232 Münster, Austria; Department of Radiology, Medical University Innsbruck, Anichstrasse 35, 6020 Innsbruck, Austria. Electronic address: andreas.lutterotti@usz.ch.
authors.forename: Andreas
authors.initials: A
authors.lastname: Lutterotti
authors.affiliation: Clinical Department of Neurology, Medical University of Innsbruck, Anichstrasse 35, 6020 Innsbruck, Austria; Clinics for Neurological Rehabilitation Münster, Groeben 700, 6232 Münster, Austria; Department of Radiology, Medical University Innsbruck, Anichstrasse 35, 6020 Innsbruck, Austria. Electronic address: bettina.kuenz@i-med.ac.at.
authors.forename: Bettina
authors.initials: B
authors.lastname: Kuenz
authors.affiliation: Clinical Department of Neurology, Medical University of Innsbruck, Anichstrasse 35, 6020 Innsbruck, Austria; Clinics for Neurological Rehabilitation Münster, Groeben 700, 6232 Münster, Austria; Department of Radiology, Medical University Innsbruck, Anichstrasse 35, 6020 Innsbruck, Austria. Electronic address: tobias.de-zordo@i-med.ac.at.
authors.forename: Tobias
authors.initials: T
authors.lastname: De Zordo
authors.affiliation: Clinical Department of Neurology, Medical University of Innsbruck, Anichstrasse 35, 6020 Innsbruck, Austria; Clinics for Neurological Rehabilitation Münster, Groeben 700, 6232 Münster, Austria; Department of Radiology, Medical University Innsbruck, Anichstrasse 35, 6020 Innsbruck, Austria. Electronic address: michael.schocke@uni-ulm.de.
authors.forename: Michael
authors.initials: M
authors.lastname: Schocke
authors.affiliation: Clinical Department of Neurology, Medical University of Innsbruck, Anichstrasse 35, 6020 Innsbruck, Austria; Clinics for Neurological Rehabilitation Münster, Groeben 700, 6232 Münster, Austria; Department of Radiology, Medical University Innsbruck, Anichstrasse 35, 6020 Innsbruck, Austria. Electronic address: susanne.glatzl@reha-muenster.at.
authors.forename: Susanne
authors.initials: S
authors.lastname: Glatzl
authors.affiliation: Clinical Department of Neurology, Medical University of Innsbruck, Anichstrasse 35, 6020 Innsbruck, Austria; Clinics for Neurological Rehabilitation Münster, Groeben 700, 6232 Münster, Austria; Department of Radiology, Medical University Innsbruck, Anichstrasse 35, 6020 Innsbruck, Austria. Electronic address: wolfgang.loescher@i-med.ac.at.
authors.forename: Wolfgang N
authors.initials: WN
authors.lastname: Löscher
authors.affiliation: Clinical Department of Neurology, Medical University of Innsbruck, Anichstrasse 35, 6020 Innsbruck, Austria; Clinics for Neurological Rehabilitation Münster, Groeben 700, 6232 Münster, Austria; Department of Radiology, Medical University Innsbruck, Anichstrasse 35, 6020 Innsbruck, Austria. Electronic address: florian.deisenhammer@tirol-kliniken.at.
authors.forename: Florian
authors.initials: F
authors.lastname: Deisenhammer
authors.affiliation: Clinical Department of Neurology, Medical University of Innsbruck, Anichstrasse 35, 6020 Innsbruck, Austria; Clinics for Neurological Rehabilitation Münster, Groeben 700, 6232 Münster, Austria; Department of Radiology, Medical University Innsbruck, Anichstrasse 35, 6020 Innsbruck, Austria. Electronic address: markus.reindl@i-med.ac.at.
authors.forename: Markus
authors.initials: M
authors.lastname: Reindl
authors.affiliation: Clinical Department of Neurology, Medical University of Innsbruck, Anichstrasse 35, 6020 Innsbruck, Austria; Clinics for Neurological Rehabilitation Münster, Groeben 700, 6232 Münster, Austria; Department of Radiology, Medical University Innsbruck, Anichstrasse 35, 6020 Innsbruck, Austria. Electronic address: thomas.berger@i-med.ac.at.
authors.forename: Thomas
authors.initials: T
authors.lastname: Berger
mesh_terms: D005260:Female; D006801:Humans; D008297:Male; D000276:Adjuvants, Immunologic / Q000627:therapeutic use; D000906:Antibodies / Q000378:metabolism; D019208:Brain-Derived Neurotrophic Factor / Q000097:blood / Q000235:genetics; D002540:Cerebral Cortex / Q000473:pathology; D004185:Disability Evaluation; D004569:Electroencephalography; D005071:Evoked Potentials / Q000187:drug effects; D000068717:Glatiramer Acetate / Q000627:therapeutic use; D008137:Longitudinal Studies; D008279:Magnetic Resonance Imaging; D009103:Multiple Sclerosis / Q000097:blood / Q000188:drug therapy; D004676:Myelin Basic Protein / Q000276:immunology; D009483:Neuropsychological Tests; D012333:RNA, Messenger / Q000378:metabolism; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D000276:Adjuvants, Immunologic; D000906:Antibodies; D019208:Brain-Derived Neurotrophic Factor; D000068717:Glatiramer Acetate; D004676:Myelin Basic Protein; D012333:RNA, Messenger
keywords: Brain derived neurotrophic factor (BDNF); Glatiramer acetate (GA); Multiple sclerosis (MS); Neuroprotection