title: The PROMESA-protocol: progression rate of multiple system atrophy under EGCG supplementation as anti-aggregation-approach.
abstract: Formation of toxic α-synuclein oligomers appears to be a key underlying pathological mechanism of synucleinopathies such as Parkinson's disease or multiple system atrophy (MSA). Given that Epigallocatechin-gallate has been shown to inhibit α-synuclein aggregation, it might represent a causal treatment option. Therefore, we set out to evaluate the safety, tolerability and a potential disease-modifying effect of Epigallocatechin-gallate in patients with MSA after 48 weeks of treatment. Power calculation was performed on existing natural history data on the progression of the Unified MSA Rating Scale as primary readout parameter. To assess the efficacy of Epigallocatechin-gallate versus placebo regarding the reduction of disease progression measured during the study period (80 % power, 5 % p level, 50 % effect size) 36 patients per group are needed. Considering a drop-out rate of 20 % a total of 86 patients will be recruited in this multicentre study. These data provide a solid rationale to investigate whether supplementation of Epigallocatechin-gallate can delay the progression of the MSA-related disability.
authors.affiliation: Department of Neurology, Klinikum Großhadern, Ludwig-Maximilians-Universität, Munich, Germany. jlevin@med.uni-muenchen.de.|German Centre for Neurodegenerative Diseases (DZNE), Feodor-Lynen Str. 17, 81377, Munich, Germany. jlevin@med.uni-muenchen.de.
authors.forename: Johannes
authors.initials: J
authors.lastname: Levin
authors.affiliation: German Centre for Neurodegenerative Diseases (DZNE), Feodor-Lynen Str. 17, 81377, Munich, Germany.|Department of Neurology, Klinikum Rechts der Isar, Technical University, Munich, Germany.
authors.forename: Sylvia
authors.initials: S
authors.lastname: Maaß
authors.affiliation: Department of Neurology, Klinikum Großhadern, Ludwig-Maximilians-Universität, Munich, Germany.
authors.forename: Madeleine
authors.initials: M
authors.lastname: Schuberth
authors.affiliation: German Centre for Neurodegenerative Diseases (DZNE), Feodor-Lynen Str. 17, 81377, Munich, Germany.|Department of Neurology, Klinikum Rechts der Isar, Technical University, Munich, Germany.
authors.forename: Gesine
authors.initials: G
authors.lastname: Respondek
authors.affiliation: NeuroCure Clinical Research Center and Clinical and Experimental Multiple Sclerosis Research Center, Department of Neurology, Charité University Medicine Berlin, Berlin, Germany.|Experimental and Clinical Research Center, Max Delbrueck Center for Molecular Medicine and Charité University Medicine Berlin, Berlin, Germany.
authors.forename: Friedemann
authors.initials: F
authors.lastname: Paul
authors.affiliation: Institute for Medical Informatics, Biometry and Epidemiology (IBE), Ludwig-Maximilians-Universität, Munich, Germany.
authors.forename: Ullrich
authors.initials: U
authors.lastname: Mansmann
authors.affiliation: Department of Neurology, Philipps Universität, Marburg, Germany.
authors.forename: Wolfgang H
authors.initials: WH
authors.lastname: Oertel
authors.affiliation: Department of Neurology, Klinikum Großhadern, Ludwig-Maximilians-Universität, Munich, Germany.|Institute of Nursing Science and Practice, Paracelsus Medical University, Salzburg, Austria.
authors.forename: Stefan
authors.initials: S
authors.lastname: Lorenzl
authors.affiliation: Department of Neurology, Medical University of Innsbruck, Innsbruck, Austria.
authors.forename: Florian
authors.initials: F
authors.lastname: Krismer
authors.affiliation: Department of Neurology, Medical University of Innsbruck, Innsbruck, Austria.
authors.forename: Klaus
authors.initials: K
authors.lastname: Seppi
authors.affiliation: Department of Neurology, Medical University of Innsbruck, Innsbruck, Austria.
authors.forename: Werner
authors.initials: W
authors.lastname: Poewe
authors.affiliation: Department of Neurology, Medical University of Innsbruck, Innsbruck, Austria.
authors.forename: Gregor
authors.initials: G
authors.lastname: Wenning
authors.affiliation: Center for Neuropathology and Prion Research, Ludwig-Maximilians-Universität, Munich, Germany.
authors.forename: Armin
authors.initials: A
authors.lastname: Giese
authors.affiliation: Department of Neurology, Klinikum Großhadern, Ludwig-Maximilians-Universität, Munich, Germany.
authors.forename: Kai
authors.initials: K
authors.lastname: Bötzel
authors.affiliation: German Centre for Neurodegenerative Diseases (DZNE), Feodor-Lynen Str. 17, 81377, Munich, Germany.|Department of Neurology, Klinikum Rechts der Isar, Technical University, Munich, Germany.
authors.forename: Günter
authors.initials: G
authors.lastname: Höglinger
mesh_terms: D002392:Catechin / Q000031:analogs & derivatives* / Q000627:therapeutic use; D018450:Disease Progression; D004311:Double-Blind Method; D006801:Humans; D019578:Multiple System Atrophy / Q000188:drug therapy*; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D012107:Research Design
chemical_list: D018696:Neuroprotective Agents; D002392:Catechin; C045651:epigallocatechin gallate
keywords: EGCG; Multiple system atrophy; Oligomer; Parkinson; Protein aggregation; α-Synuclein
references.citation: AJNR Am J Neuroradiol. 2012 Feb;33(2):266-73
references.pmid: 22051807
references.citation: J Neuroimaging. 2010 Jul;20(3):260-6
references.pmid: 19187475
references.citation: J Neurol Sci. 2003 Dec 15;216(1):163-7
references.pmid: 14607318
references.citation: EPMA J. 2013 Feb 18;4(1):5
references.pmid: 23418936
references.citation: Neuroimage. 2010 Feb 1;49(3):2216-24
references.pmid: 19878722
references.citation: Neurology. 2008 Aug 26;71(9):670-6
references.pmid: 18725592
references.citation: Ann N Y Acad Sci. 2004 Mar;1012:306-25
references.pmid: 15105275
references.citation: Mol Neurodegener. 2015 Mar 19;10:10
references.pmid: 25886309
references.citation: Lancet Neurol. 2015 Jul;14(7):710-9
references.pmid: 26025783
references.citation: Acta Neuropathol. 2013 Jun;125(6):795-813
references.pmid: 23604588
references.citation: N Engl J Med. 2015 Jan 15;372(3):249-63
references.pmid: 25587949
references.citation: Proc Natl Acad Sci U S A. 2013 Nov 26;110(48):19555-60
references.pmid: 24218576
references.citation: Neuroimage. 2007 Jul 15;36(4):1086-95
references.pmid: 17512219
references.citation: Lancet Neurol. 2015 Aug;14 (8):855-866
references.pmid: 26050140
references.citation: FEBS Lett. 2011 Apr 20;585(8):1113-20
references.pmid: 21443877
references.citation: J Biol Chem. 2009 Apr 10;284(15):10211-22
references.pmid: 19203998
references.citation: Proc Natl Acad Sci U S A. 2010 Apr 27;107(17):7710-5
references.pmid: 20385841
references.citation: Lancet Neurol. 2014 Mar;13(3):268-75
references.pmid: 24507091
references.citation: Am J Epidemiol. 2002 Apr 15;155(8):732-8
references.pmid: 11943691
references.citation: Eur J Clin Pharmacol. 2009 Apr;65(4):331-41
references.pmid: 19198822
references.citation: Mov Disord. 2008 Apr 30;23 (6):797-803
references.pmid: 18307243
references.citation: Lancet Neurol. 2015 Feb;14(2):145-52
references.pmid: 25498732
references.citation: J Neurochem. 2001 Sep;78(5):1073-82
references.pmid: 11553681
references.citation: J Agric Food Chem. 2007 Feb 21;55(4):1517-24
references.pmid: 17256961
references.citation: Int J Vitam Nutr Res. 2004 Jul;74(4):269-78
references.pmid: 15580809
references.citation: Mov Disord. 2007 Nov 15;22(15):2242-8
references.pmid: 17712848
references.citation: Lancet Neurol. 2013 Mar;12(3):264-74
references.pmid: 23391524
references.citation: Mov Disord. 2010 Jan 15;25(1):97-107
references.pmid: 20014118
references.citation: Neurobiol Dis. 2014 Jul;67:133-9
references.pmid: 24727096
references.citation: Mov Disord. 2004 Dec;19(12):1391-402
references.pmid: 15452868
references.citation: J Neurosci. 2010 May 5;30(18):6236-46
references.pmid: 20445049
references.citation: J Am Chem Soc. 2013 May 22;135(20):7503-10
references.pmid: 23611538
references.citation: Acta Neuropathol. 2014 May;127(5):779-80
references.pmid: 24615514