Minocycline 1‐year therapy in multiple‐system‐atrophy: Effect on clinical symptoms and [11C] (R)‐PK11195 PET (MEMSA‐trial)
Identifieur interne : 000058 ( Istex/Corpus ); précédent : 000057; suivant : 000059Minocycline 1‐year therapy in multiple‐system‐atrophy: Effect on clinical symptoms and [11C] (R)‐PK11195 PET (MEMSA‐trial)
Auteurs : Richard Dodel ; Annika Spottke ; Alexander Gerhard ; Alexander Reuss ; Sylvia Reinecker ; Nicole Schimke ; Claudia Trenkwalder ; Friederike Sixel-Döring ; Birgit Herting ; Christoph Kamm ; Thomas Gasser ; Martin Sawires ; Felix Geser ; Martin Köllensperger ; Klaus Seppi ; Manja Kloss ; Martin Krause ; Christine Daniels ; Günther Deuschl ; Silke Böttger ; Markus Naumann ; Axel Lipp ; Doreen Gruber ; Andreas Kupsch ; Yansheng Du ; Federico Turkheimer ; David J. Brooks ; Thomas Klockgether ; Werner Poewe ; Gregor Wenning ; Carmen Schade-Brittinger ; Wolfgang H. Oertel ; Karla EggertSource :
- Movement Disorders [ 0885-3185 ] ; 2010-01-15.
English descriptors
- KwdEn :
Abstract
The aim of the study was to investigate the efficacy of the antibiotic minocycline as a drug treatment in patients with Multiple‐System‐Atrophy Parkinson‐type (MSA‐P). Sixty‐three patients were randomized to minocycline 200 mg/d (n = 32) or a matching placebo (n = 31). The primary outcome variable was the change in the value of the motor score of the Unified Multiple‐System‐Atrophy Rating‐Scale (UMSARSII) from baseline to 48 weeks. Secondary outcome variables included subscores and individual Parkinsonian symptoms as determined by the UMSARS and the Unified‐Parkinson's‐Disease Rating‐Scale (UPDRS). Health‐related quality of life (HrQoL) was assessed using the EQ‐5D and SF‐12. “Progression rate” was assumed to be reflected in the change in motor function over 48 weeks. At 24 weeks and 48 weeks of follow‐up, there was a significant deterioration in motor scores in both groups, but neither the change in UMSARSII nor in UPDRSIII differed significantly between treatment groups, i.e. “progression rate” was considered to be similar in both treatment arms. HrQoL did not differ among the two treatment arms. In a small subgroup of patients (n = 8; minocycline = 3, placebo = 5)[11C](R)‐PK11195‐PET was performed. The three patients in the minocycline group had an attenuated mean increase in microglial activation as compared to the placebo group (P = 0.07) and in two of them individually showed decreased [11C](R)‐PK11195 binding actually decreased. These preliminary PET‐data suggest that minocycline may interfere with microglial activation. The relevance of this observation requires further investigation. This prospective, 48 week, randomized, double‐blind, multinational study failed to show a clinical effect of minocycline on symptom severity as assessed by clinical motor function. © 2009 Movement Disorder Society
Url:
DOI: 10.1002/mds.22732
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<author><name sortKey="Dodel, Richard" sort="Dodel, Richard" uniqKey="Dodel R" first="Richard" last="Dodel">Richard Dodel</name>
<affiliation><mods:affiliation>Department of Neurology, Philipps‐University of Marburg, Germany</mods:affiliation>
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<affiliation><mods:affiliation>Department of Neurology, University of Bonn, Germany</mods:affiliation>
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<author><name sortKey="Spottke, Annika" sort="Spottke, Annika" uniqKey="Spottke A" first="Annika" last="Spottke">Annika Spottke</name>
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<author><name sortKey="Gerhard, Alexander" sort="Gerhard, Alexander" uniqKey="Gerhard A" first="Alexander" last="Gerhard">Alexander Gerhard</name>
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<affiliation><mods:affiliation>IMRC Clinical Sciences Centre and Division of Neuroscience, Faculty of Medicine, Imperial College; London, United Kingdom</mods:affiliation>
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<author><name sortKey="Reuss, Alexander" sort="Reuss, Alexander" uniqKey="Reuss A" first="Alexander" last="Reuss">Alexander Reuss</name>
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<author><name sortKey="Reinecker, Sylvia" sort="Reinecker, Sylvia" uniqKey="Reinecker S" first="Sylvia" last="Reinecker">Sylvia Reinecker</name>
<affiliation><mods:affiliation>Coordinating Center for Clinical Trials, Philipps‐University of Marburg, Germany</mods:affiliation>
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<author><name sortKey="Schimke, Nicole" sort="Schimke, Nicole" uniqKey="Schimke N" first="Nicole" last="Schimke">Nicole Schimke</name>
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<author><name sortKey="Trenkwalder, Claudia" sort="Trenkwalder, Claudia" uniqKey="Trenkwalder C" first="Claudia" last="Trenkwalder">Claudia Trenkwalder</name>
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<author><name sortKey="Sixel Ring, Friederike" sort="Sixel Ring, Friederike" uniqKey="Sixel Ring F" first="Friederike" last="Sixel-Döring">Friederike Sixel-Döring</name>
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<author><name sortKey="Herting, Birgit" sort="Herting, Birgit" uniqKey="Herting B" first="Birgit" last="Herting">Birgit Herting</name>
<affiliation><mods:affiliation>Department of Neurology, Dresden University of Technology, Germany</mods:affiliation>
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<author><name sortKey="Kamm, Christoph" sort="Kamm, Christoph" uniqKey="Kamm C" first="Christoph" last="Kamm">Christoph Kamm</name>
<affiliation><mods:affiliation>Hertie‐Institute, University of Tübingen, Germany</mods:affiliation>
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<affiliation><mods:affiliation>Department of Neurology, University of Rostock, Germany</mods:affiliation>
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<author><name sortKey="Gasser, Thomas" sort="Gasser, Thomas" uniqKey="Gasser T" first="Thomas" last="Gasser">Thomas Gasser</name>
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<author><name sortKey="Sawires, Martin" sort="Sawires, Martin" uniqKey="Sawires M" first="Martin" last="Sawires">Martin Sawires</name>
<affiliation><mods:affiliation>Department of Neurology, Medical University of Innsbruck, Austria</mods:affiliation>
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<author><name sortKey="Geser, Felix" sort="Geser, Felix" uniqKey="Geser F" first="Felix" last="Geser">Felix Geser</name>
<affiliation><mods:affiliation>Department of Neurology, Medical University of Innsbruck, Austria</mods:affiliation>
</affiliation>
<affiliation><mods:affiliation>European MSA Study Group, Innsbruck Medical University, Austria</mods:affiliation>
</affiliation>
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<author><name sortKey="Kollensperger, Martin" sort="Kollensperger, Martin" uniqKey="Kollensperger M" first="Martin" last="Köllensperger">Martin Köllensperger</name>
<affiliation><mods:affiliation>Department of Neurology, Medical University of Innsbruck, Austria</mods:affiliation>
</affiliation>
</author>
<author><name sortKey="Seppi, Klaus" sort="Seppi, Klaus" uniqKey="Seppi K" first="Klaus" last="Seppi">Klaus Seppi</name>
<affiliation><mods:affiliation>Department of Neurology, Medical University of Innsbruck, Austria</mods:affiliation>
</affiliation>
<affiliation><mods:affiliation>European MSA Study Group, Innsbruck Medical University, Austria</mods:affiliation>
</affiliation>
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<author><name sortKey="Kloss, Manja" sort="Kloss, Manja" uniqKey="Kloss M" first="Manja" last="Kloss">Manja Kloss</name>
<affiliation><mods:affiliation>Department of Neurology, University of Heidelberg, Germany</mods:affiliation>
</affiliation>
</author>
<author><name sortKey="Krause, Martin" sort="Krause, Martin" uniqKey="Krause M" first="Martin" last="Krause">Martin Krause</name>
<affiliation><mods:affiliation>Department of Neurology, University of Heidelberg, Germany</mods:affiliation>
</affiliation>
</author>
<author><name sortKey="Daniels, Christine" sort="Daniels, Christine" uniqKey="Daniels C" first="Christine" last="Daniels">Christine Daniels</name>
<affiliation><mods:affiliation>Department of Neurology, University of Kiel, Germany</mods:affiliation>
</affiliation>
</author>
<author><name sortKey="Deuschl, Gunther" sort="Deuschl, Gunther" uniqKey="Deuschl G" first="Günther" last="Deuschl">Günther Deuschl</name>
<affiliation><mods:affiliation>Department of Neurology, University of Kiel, Germany</mods:affiliation>
</affiliation>
</author>
<author><name sortKey="Bottger, Silke" sort="Bottger, Silke" uniqKey="Bottger S" first="Silke" last="Böttger">Silke Böttger</name>
<affiliation><mods:affiliation>Department of Neurology, University of Würzburg, Germany</mods:affiliation>
</affiliation>
</author>
<author><name sortKey="Naumann, Markus" sort="Naumann, Markus" uniqKey="Naumann M" first="Markus" last="Naumann">Markus Naumann</name>
<affiliation><mods:affiliation>Department of Neurology, University of Würzburg, Germany</mods:affiliation>
</affiliation>
</author>
<author><name sortKey="Lipp, Axel" sort="Lipp, Axel" uniqKey="Lipp A" first="Axel" last="Lipp">Axel Lipp</name>
<affiliation><mods:affiliation>Wolfson Molecular Imaging Centre, The University of Manchester, United Kingdom</mods:affiliation>
</affiliation>
</author>
<author><name sortKey="Gruber, Doreen" sort="Gruber, Doreen" uniqKey="Gruber D" first="Doreen" last="Gruber">Doreen Gruber</name>
<affiliation><mods:affiliation>Department of Neurology, University of Berlin, Germany</mods:affiliation>
</affiliation>
</author>
<author><name sortKey="Kupsch, Andreas" sort="Kupsch, Andreas" uniqKey="Kupsch A" first="Andreas" last="Kupsch">Andreas Kupsch</name>
<affiliation><mods:affiliation>Department of Neurology, University of Berlin, Germany</mods:affiliation>
</affiliation>
</author>
<author><name sortKey="Du, Yansheng" sort="Du, Yansheng" uniqKey="Du Y" first="Yansheng" last="Du">Yansheng Du</name>
<affiliation><mods:affiliation>Department of Neurology, Indiana University Medical School, Indianapolis, Indiana, USA</mods:affiliation>
</affiliation>
</author>
<author><name sortKey="Turkheimer, Federico" sort="Turkheimer, Federico" uniqKey="Turkheimer F" first="Federico" last="Turkheimer">Federico Turkheimer</name>
<affiliation><mods:affiliation>IMRC Clinical Sciences Centre and Division of Neuroscience, Faculty of Medicine, Imperial College; London, United Kingdom</mods:affiliation>
</affiliation>
</author>
<author><name sortKey="Brooks, David J" sort="Brooks, David J" uniqKey="Brooks D" first="David J." last="Brooks">David J. Brooks</name>
<affiliation><mods:affiliation>IMRC Clinical Sciences Centre and Division of Neuroscience, Faculty of Medicine, Imperial College; London, United Kingdom</mods:affiliation>
</affiliation>
</author>
<author><name sortKey="Klockgether, Thomas" sort="Klockgether, Thomas" uniqKey="Klockgether T" first="Thomas" last="Klockgether">Thomas Klockgether</name>
<affiliation><mods:affiliation>Department of Neurology, University of Bonn, Germany</mods:affiliation>
</affiliation>
</author>
<author><name sortKey="Poewe, Werner" sort="Poewe, Werner" uniqKey="Poewe W" first="Werner" last="Poewe">Werner Poewe</name>
<affiliation><mods:affiliation>Department of Neurology, Medical University of Innsbruck, Austria</mods:affiliation>
</affiliation>
<affiliation><mods:affiliation>European MSA Study Group, Innsbruck Medical University, Austria</mods:affiliation>
</affiliation>
</author>
<author><name sortKey="Wenning, Gregor" sort="Wenning, Gregor" uniqKey="Wenning G" first="Gregor" last="Wenning">Gregor Wenning</name>
<affiliation><mods:affiliation>Department of Neurology, Medical University of Innsbruck, Austria</mods:affiliation>
</affiliation>
<affiliation><mods:affiliation>European MSA Study Group, Innsbruck Medical University, Austria</mods:affiliation>
</affiliation>
</author>
<author><name sortKey="Schade Rittinger, Carmen" sort="Schade Rittinger, Carmen" uniqKey="Schade Rittinger C" first="Carmen" last="Schade-Brittinger">Carmen Schade-Brittinger</name>
<affiliation><mods:affiliation>Coordinating Center for Clinical Trials, Philipps‐University of Marburg, Germany</mods:affiliation>
</affiliation>
</author>
<author><name sortKey="Oertel, Wolfgang H" sort="Oertel, Wolfgang H" uniqKey="Oertel W" first="Wolfgang H." last="Oertel">Wolfgang H. Oertel</name>
<affiliation><mods:affiliation>Department of Neurology, Philipps‐University of Marburg, Germany</mods:affiliation>
</affiliation>
<affiliation><mods:affiliation>Competence Network Parkinson‐Syndrome, Philipps‐University of Marburg, Germany</mods:affiliation>
</affiliation>
</author>
<author><name sortKey="Eggert, Karla" sort="Eggert, Karla" uniqKey="Eggert K" first="Karla" last="Eggert">Karla Eggert</name>
<affiliation><mods:affiliation>Department of Neurology, Philipps‐University of Marburg, Germany</mods:affiliation>
</affiliation>
<affiliation><mods:affiliation>Competence Network Parkinson‐Syndrome, Philipps‐University of Marburg, Germany</mods:affiliation>
</affiliation>
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<sourceDesc><biblStruct><analytic><title level="a" type="main" xml:lang="en">Minocycline 1‐year therapy in multiple‐system‐atrophy: Effect on clinical symptoms and [11C] (R)‐PK11195 PET (MEMSA‐trial)</title>
<author><name sortKey="Dodel, Richard" sort="Dodel, Richard" uniqKey="Dodel R" first="Richard" last="Dodel">Richard Dodel</name>
<affiliation><mods:affiliation>Department of Neurology, Philipps‐University of Marburg, Germany</mods:affiliation>
</affiliation>
<affiliation><mods:affiliation>Department of Neurology, University of Bonn, Germany</mods:affiliation>
</affiliation>
</author>
<author><name sortKey="Spottke, Annika" sort="Spottke, Annika" uniqKey="Spottke A" first="Annika" last="Spottke">Annika Spottke</name>
<affiliation><mods:affiliation>Department of Neurology, University of Bonn, Germany</mods:affiliation>
</affiliation>
</author>
<author><name sortKey="Gerhard, Alexander" sort="Gerhard, Alexander" uniqKey="Gerhard A" first="Alexander" last="Gerhard">Alexander Gerhard</name>
<affiliation><mods:affiliation>Wolfson Molecular Imaging Centre, The University of Manchester, United Kingdom</mods:affiliation>
</affiliation>
<affiliation><mods:affiliation>IMRC Clinical Sciences Centre and Division of Neuroscience, Faculty of Medicine, Imperial College; London, United Kingdom</mods:affiliation>
</affiliation>
</author>
<author><name sortKey="Reuss, Alexander" sort="Reuss, Alexander" uniqKey="Reuss A" first="Alexander" last="Reuss">Alexander Reuss</name>
<affiliation><mods:affiliation>Coordinating Center for Clinical Trials, Philipps‐University of Marburg, Germany</mods:affiliation>
</affiliation>
</author>
<author><name sortKey="Reinecker, Sylvia" sort="Reinecker, Sylvia" uniqKey="Reinecker S" first="Sylvia" last="Reinecker">Sylvia Reinecker</name>
<affiliation><mods:affiliation>Coordinating Center for Clinical Trials, Philipps‐University of Marburg, Germany</mods:affiliation>
</affiliation>
</author>
<author><name sortKey="Schimke, Nicole" sort="Schimke, Nicole" uniqKey="Schimke N" first="Nicole" last="Schimke">Nicole Schimke</name>
<affiliation><mods:affiliation>Department of Neurology, Philipps‐University of Marburg, Germany</mods:affiliation>
</affiliation>
</author>
<author><name sortKey="Trenkwalder, Claudia" sort="Trenkwalder, Claudia" uniqKey="Trenkwalder C" first="Claudia" last="Trenkwalder">Claudia Trenkwalder</name>
<affiliation><mods:affiliation>Paracelsus‐Elena‐Clinic Kassel, Germany</mods:affiliation>
</affiliation>
</author>
<author><name sortKey="Sixel Ring, Friederike" sort="Sixel Ring, Friederike" uniqKey="Sixel Ring F" first="Friederike" last="Sixel-Döring">Friederike Sixel-Döring</name>
<affiliation><mods:affiliation>Paracelsus‐Elena‐Clinic Kassel, Germany</mods:affiliation>
</affiliation>
</author>
<author><name sortKey="Herting, Birgit" sort="Herting, Birgit" uniqKey="Herting B" first="Birgit" last="Herting">Birgit Herting</name>
<affiliation><mods:affiliation>Department of Neurology, Dresden University of Technology, Germany</mods:affiliation>
</affiliation>
</author>
<author><name sortKey="Kamm, Christoph" sort="Kamm, Christoph" uniqKey="Kamm C" first="Christoph" last="Kamm">Christoph Kamm</name>
<affiliation><mods:affiliation>Hertie‐Institute, University of Tübingen, Germany</mods:affiliation>
</affiliation>
<affiliation><mods:affiliation>Department of Neurology, University of Rostock, Germany</mods:affiliation>
</affiliation>
</author>
<author><name sortKey="Gasser, Thomas" sort="Gasser, Thomas" uniqKey="Gasser T" first="Thomas" last="Gasser">Thomas Gasser</name>
<affiliation><mods:affiliation>Hertie‐Institute, University of Tübingen, Germany</mods:affiliation>
</affiliation>
</author>
<author><name sortKey="Sawires, Martin" sort="Sawires, Martin" uniqKey="Sawires M" first="Martin" last="Sawires">Martin Sawires</name>
<affiliation><mods:affiliation>Department of Neurology, Medical University of Innsbruck, Austria</mods:affiliation>
</affiliation>
</author>
<author><name sortKey="Geser, Felix" sort="Geser, Felix" uniqKey="Geser F" first="Felix" last="Geser">Felix Geser</name>
<affiliation><mods:affiliation>Department of Neurology, Medical University of Innsbruck, Austria</mods:affiliation>
</affiliation>
<affiliation><mods:affiliation>European MSA Study Group, Innsbruck Medical University, Austria</mods:affiliation>
</affiliation>
</author>
<author><name sortKey="Kollensperger, Martin" sort="Kollensperger, Martin" uniqKey="Kollensperger M" first="Martin" last="Köllensperger">Martin Köllensperger</name>
<affiliation><mods:affiliation>Department of Neurology, Medical University of Innsbruck, Austria</mods:affiliation>
</affiliation>
</author>
<author><name sortKey="Seppi, Klaus" sort="Seppi, Klaus" uniqKey="Seppi K" first="Klaus" last="Seppi">Klaus Seppi</name>
<affiliation><mods:affiliation>Department of Neurology, Medical University of Innsbruck, Austria</mods:affiliation>
</affiliation>
<affiliation><mods:affiliation>European MSA Study Group, Innsbruck Medical University, Austria</mods:affiliation>
</affiliation>
</author>
<author><name sortKey="Kloss, Manja" sort="Kloss, Manja" uniqKey="Kloss M" first="Manja" last="Kloss">Manja Kloss</name>
<affiliation><mods:affiliation>Department of Neurology, University of Heidelberg, Germany</mods:affiliation>
</affiliation>
</author>
<author><name sortKey="Krause, Martin" sort="Krause, Martin" uniqKey="Krause M" first="Martin" last="Krause">Martin Krause</name>
<affiliation><mods:affiliation>Department of Neurology, University of Heidelberg, Germany</mods:affiliation>
</affiliation>
</author>
<author><name sortKey="Daniels, Christine" sort="Daniels, Christine" uniqKey="Daniels C" first="Christine" last="Daniels">Christine Daniels</name>
<affiliation><mods:affiliation>Department of Neurology, University of Kiel, Germany</mods:affiliation>
</affiliation>
</author>
<author><name sortKey="Deuschl, Gunther" sort="Deuschl, Gunther" uniqKey="Deuschl G" first="Günther" last="Deuschl">Günther Deuschl</name>
<affiliation><mods:affiliation>Department of Neurology, University of Kiel, Germany</mods:affiliation>
</affiliation>
</author>
<author><name sortKey="Bottger, Silke" sort="Bottger, Silke" uniqKey="Bottger S" first="Silke" last="Böttger">Silke Böttger</name>
<affiliation><mods:affiliation>Department of Neurology, University of Würzburg, Germany</mods:affiliation>
</affiliation>
</author>
<author><name sortKey="Naumann, Markus" sort="Naumann, Markus" uniqKey="Naumann M" first="Markus" last="Naumann">Markus Naumann</name>
<affiliation><mods:affiliation>Department of Neurology, University of Würzburg, Germany</mods:affiliation>
</affiliation>
</author>
<author><name sortKey="Lipp, Axel" sort="Lipp, Axel" uniqKey="Lipp A" first="Axel" last="Lipp">Axel Lipp</name>
<affiliation><mods:affiliation>Wolfson Molecular Imaging Centre, The University of Manchester, United Kingdom</mods:affiliation>
</affiliation>
</author>
<author><name sortKey="Gruber, Doreen" sort="Gruber, Doreen" uniqKey="Gruber D" first="Doreen" last="Gruber">Doreen Gruber</name>
<affiliation><mods:affiliation>Department of Neurology, University of Berlin, Germany</mods:affiliation>
</affiliation>
</author>
<author><name sortKey="Kupsch, Andreas" sort="Kupsch, Andreas" uniqKey="Kupsch A" first="Andreas" last="Kupsch">Andreas Kupsch</name>
<affiliation><mods:affiliation>Department of Neurology, University of Berlin, Germany</mods:affiliation>
</affiliation>
</author>
<author><name sortKey="Du, Yansheng" sort="Du, Yansheng" uniqKey="Du Y" first="Yansheng" last="Du">Yansheng Du</name>
<affiliation><mods:affiliation>Department of Neurology, Indiana University Medical School, Indianapolis, Indiana, USA</mods:affiliation>
</affiliation>
</author>
<author><name sortKey="Turkheimer, Federico" sort="Turkheimer, Federico" uniqKey="Turkheimer F" first="Federico" last="Turkheimer">Federico Turkheimer</name>
<affiliation><mods:affiliation>IMRC Clinical Sciences Centre and Division of Neuroscience, Faculty of Medicine, Imperial College; London, United Kingdom</mods:affiliation>
</affiliation>
</author>
<author><name sortKey="Brooks, David J" sort="Brooks, David J" uniqKey="Brooks D" first="David J." last="Brooks">David J. Brooks</name>
<affiliation><mods:affiliation>IMRC Clinical Sciences Centre and Division of Neuroscience, Faculty of Medicine, Imperial College; London, United Kingdom</mods:affiliation>
</affiliation>
</author>
<author><name sortKey="Klockgether, Thomas" sort="Klockgether, Thomas" uniqKey="Klockgether T" first="Thomas" last="Klockgether">Thomas Klockgether</name>
<affiliation><mods:affiliation>Department of Neurology, University of Bonn, Germany</mods:affiliation>
</affiliation>
</author>
<author><name sortKey="Poewe, Werner" sort="Poewe, Werner" uniqKey="Poewe W" first="Werner" last="Poewe">Werner Poewe</name>
<affiliation><mods:affiliation>Department of Neurology, Medical University of Innsbruck, Austria</mods:affiliation>
</affiliation>
<affiliation><mods:affiliation>European MSA Study Group, Innsbruck Medical University, Austria</mods:affiliation>
</affiliation>
</author>
<author><name sortKey="Wenning, Gregor" sort="Wenning, Gregor" uniqKey="Wenning G" first="Gregor" last="Wenning">Gregor Wenning</name>
<affiliation><mods:affiliation>Department of Neurology, Medical University of Innsbruck, Austria</mods:affiliation>
</affiliation>
<affiliation><mods:affiliation>European MSA Study Group, Innsbruck Medical University, Austria</mods:affiliation>
</affiliation>
</author>
<author><name sortKey="Schade Rittinger, Carmen" sort="Schade Rittinger, Carmen" uniqKey="Schade Rittinger C" first="Carmen" last="Schade-Brittinger">Carmen Schade-Brittinger</name>
<affiliation><mods:affiliation>Coordinating Center for Clinical Trials, Philipps‐University of Marburg, Germany</mods:affiliation>
</affiliation>
</author>
<author><name sortKey="Oertel, Wolfgang H" sort="Oertel, Wolfgang H" uniqKey="Oertel W" first="Wolfgang H." last="Oertel">Wolfgang H. Oertel</name>
<affiliation><mods:affiliation>Department of Neurology, Philipps‐University of Marburg, Germany</mods:affiliation>
</affiliation>
<affiliation><mods:affiliation>Competence Network Parkinson‐Syndrome, Philipps‐University of Marburg, Germany</mods:affiliation>
</affiliation>
</author>
<author><name sortKey="Eggert, Karla" sort="Eggert, Karla" uniqKey="Eggert K" first="Karla" last="Eggert">Karla Eggert</name>
<affiliation><mods:affiliation>Department of Neurology, Philipps‐University of Marburg, Germany</mods:affiliation>
</affiliation>
<affiliation><mods:affiliation>Competence Network Parkinson‐Syndrome, Philipps‐University of Marburg, Germany</mods:affiliation>
</affiliation>
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<series><title level="j">Movement Disorders</title>
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<front><div type="abstract" xml:lang="en">The aim of the study was to investigate the efficacy of the antibiotic minocycline as a drug treatment in patients with Multiple‐System‐Atrophy Parkinson‐type (MSA‐P). Sixty‐three patients were randomized to minocycline 200 mg/d (n = 32) or a matching placebo (n = 31). The primary outcome variable was the change in the value of the motor score of the Unified Multiple‐System‐Atrophy Rating‐Scale (UMSARSII) from baseline to 48 weeks. Secondary outcome variables included subscores and individual Parkinsonian symptoms as determined by the UMSARS and the Unified‐Parkinson's‐Disease Rating‐Scale (UPDRS). Health‐related quality of life (HrQoL) was assessed using the EQ‐5D and SF‐12. “Progression rate” was assumed to be reflected in the change in motor function over 48 weeks. At 24 weeks and 48 weeks of follow‐up, there was a significant deterioration in motor scores in both groups, but neither the change in UMSARSII nor in UPDRSIII differed significantly between treatment groups, i.e. “progression rate” was considered to be similar in both treatment arms. HrQoL did not differ among the two treatment arms. In a small subgroup of patients (n = 8; minocycline = 3, placebo = 5)[11C](R)‐PK11195‐PET was performed. The three patients in the minocycline group had an attenuated mean increase in microglial activation as compared to the placebo group (P = 0.07) and in two of them individually showed decreased [11C](R)‐PK11195 binding actually decreased. These preliminary PET‐data suggest that minocycline may interfere with microglial activation. The relevance of this observation requires further investigation. This prospective, 48 week, randomized, double‐blind, multinational study failed to show a clinical effect of minocycline on symptom severity as assessed by clinical motor function. © 2009 Movement Disorder Society</div>
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<author><json:item><name>Richard Dodel MD</name>
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<json:item><name>Alexander Gerhard MD</name>
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<json:item><name>Birgit Herting MD</name>
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<json:item><name>Martin Sawires MD</name>
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<json:item><name>Klaus Seppi MD</name>
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<json:item><name>Manja Kloss MD</name>
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<json:item><name>Martin Krause MD</name>
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<json:item><name>Silke Böttger MD</name>
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<json:item><name>Markus Naumann MD</name>
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<json:item><name>Axel Lipp MD</name>
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<json:item><name>David J. Brooks MD</name>
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<json:item><name>Thomas Klockgether MD</name>
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<abstract>The aim of the study was to investigate the efficacy of the antibiotic minocycline as a drug treatment in patients with Multiple‐System‐Atrophy Parkinson‐type (MSA‐P). Sixty‐three patients were randomized to minocycline 200 mg/d (n = 32) or a matching placebo (n = 31). The primary outcome variable was the change in the value of the motor score of the Unified Multiple‐System‐Atrophy Rating‐Scale (UMSARSII) from baseline to 48 weeks. Secondary outcome variables included subscores and individual Parkinsonian symptoms as determined by the UMSARS and the Unified‐Parkinson's‐Disease Rating‐Scale (UPDRS). Health‐related quality of life (HrQoL) was assessed using the EQ‐5D and SF‐12. “Progression rate” was assumed to be reflected in the change in motor function over 48 weeks. At 24 weeks and 48 weeks of follow‐up, there was a significant deterioration in motor scores in both groups, but neither the change in UMSARSII nor in UPDRSIII differed significantly between treatment groups, i.e. “progression rate” was considered to be similar in both treatment arms. HrQoL did not differ among the two treatment arms. In a small subgroup of patients (n = 8; minocycline = 3, placebo = 5)[11C](R)‐PK11195‐PET was performed. The three patients in the minocycline group had an attenuated mean increase in microglial activation as compared to the placebo group (P = 0.07) and in two of them individually showed decreased [11C](R)‐PK11195 binding actually decreased. These preliminary PET‐data suggest that minocycline may interfere with microglial activation. The relevance of this observation requires further investigation. This prospective, 48 week, randomized, double‐blind, multinational study failed to show a clinical effect of minocycline on symptom severity as assessed by clinical motor function. © 2009 Movement Disorder Society</abstract>
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<notesStmt><note type="content">*Potential conflict of interest: The authors report no conflicts of interest and have no financial disclosures to make in respect to this article.</note>
<note>German Ministry of Education and Research - No. BMBF Nr. 01GI9901; No. 01GI0201; No. 01GI040;</note>
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<author><persName><forename type="first">Richard</forename>
<surname>Dodel</surname>
<roleName type="degree">MD</roleName>
</persName>
<note type="biography">Richard Dodel, Annika Spottke, Alexander Gerhard, Alexander Reuss, Wolfgang H. Oertel, and Karla Eggert contributed equally to this work.</note>
<affiliation>Richard Dodel, Annika Spottke, Alexander Gerhard, Alexander Reuss, Wolfgang H. Oertel, and Karla Eggert contributed equally to this work.</affiliation>
<note type="correspondence"><p>Correspondence: Department of Neurology, Philipps‐University Marburg, Rudolf‐Bultmannstr. 8, 35039 Marburg, Germany</p>
</note>
<affiliation>Department of Neurology, Philipps‐University of Marburg, Germany</affiliation>
<affiliation>Department of Neurology, University of Bonn, Germany</affiliation>
</author>
<author><persName><forename type="first">Annika</forename>
<surname>Spottke</surname>
<roleName type="degree">MD</roleName>
</persName>
<note type="biography">Richard Dodel, Annika Spottke, Alexander Gerhard, Alexander Reuss, Wolfgang H. Oertel, and Karla Eggert contributed equally to this work.</note>
<affiliation>Richard Dodel, Annika Spottke, Alexander Gerhard, Alexander Reuss, Wolfgang H. Oertel, and Karla Eggert contributed equally to this work.</affiliation>
<affiliation>Department of Neurology, University of Bonn, Germany</affiliation>
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<author><persName><forename type="first">Alexander</forename>
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<note type="biography">Richard Dodel, Annika Spottke, Alexander Gerhard, Alexander Reuss, Wolfgang H. Oertel, and Karla Eggert contributed equally to this work.</note>
<affiliation>Richard Dodel, Annika Spottke, Alexander Gerhard, Alexander Reuss, Wolfgang H. Oertel, and Karla Eggert contributed equally to this work.</affiliation>
<affiliation>Wolfson Molecular Imaging Centre, The University of Manchester, United Kingdom</affiliation>
<affiliation>IMRC Clinical Sciences Centre and Division of Neuroscience, Faculty of Medicine, Imperial College; London, United Kingdom</affiliation>
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<author><persName><forename type="first">Alexander</forename>
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<note type="biography">Richard Dodel, Annika Spottke, Alexander Gerhard, Alexander Reuss, Wolfgang H. Oertel, and Karla Eggert contributed equally to this work.</note>
<affiliation>Richard Dodel, Annika Spottke, Alexander Gerhard, Alexander Reuss, Wolfgang H. Oertel, and Karla Eggert contributed equally to this work.</affiliation>
<affiliation>Coordinating Center for Clinical Trials, Philipps‐University of Marburg, Germany</affiliation>
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<author><persName><forename type="first">Sylvia</forename>
<surname>Reinecker</surname>
<roleName type="degree">MSc</roleName>
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<affiliation>Coordinating Center for Clinical Trials, Philipps‐University of Marburg, Germany</affiliation>
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<author><persName><forename type="first">Nicole</forename>
<surname>Schimke</surname>
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<affiliation>Department of Neurology, Philipps‐University of Marburg, Germany</affiliation>
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<author><persName><forename type="first">Claudia</forename>
<surname>Trenkwalder</surname>
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<affiliation>Paracelsus‐Elena‐Clinic Kassel, Germany</affiliation>
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<author><persName><forename type="first">Friederike</forename>
<surname>Sixel‐Döring</surname>
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<affiliation>Paracelsus‐Elena‐Clinic Kassel, Germany</affiliation>
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<author><persName><forename type="first">Birgit</forename>
<surname>Herting</surname>
<roleName type="degree">MD</roleName>
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<affiliation>Department of Neurology, Dresden University of Technology, Germany</affiliation>
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<author><persName><forename type="first">Christoph</forename>
<surname>Kamm</surname>
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<affiliation>Hertie‐Institute, University of Tübingen, Germany</affiliation>
<affiliation>Department of Neurology, University of Rostock, Germany</affiliation>
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<author><persName><forename type="first">Thomas</forename>
<surname>Gasser</surname>
<roleName type="degree">MD</roleName>
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<affiliation>Hertie‐Institute, University of Tübingen, Germany</affiliation>
</author>
<author><persName><forename type="first">Martin</forename>
<surname>Sawires</surname>
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<affiliation>Department of Neurology, Medical University of Innsbruck, Austria</affiliation>
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<author><persName><forename type="first">Felix</forename>
<surname>Geser</surname>
<roleName type="degree">MD, PhD</roleName>
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<affiliation>Department of Neurology, Medical University of Innsbruck, Austria</affiliation>
<affiliation>European MSA Study Group, Innsbruck Medical University, Austria</affiliation>
</author>
<author><persName><forename type="first">Martin</forename>
<surname>Köllensperger</surname>
<roleName type="degree">MD</roleName>
</persName>
<affiliation>Department of Neurology, Medical University of Innsbruck, Austria</affiliation>
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<author><persName><forename type="first">Klaus</forename>
<surname>Seppi</surname>
<roleName type="degree">MD</roleName>
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<affiliation>Department of Neurology, Medical University of Innsbruck, Austria</affiliation>
<affiliation>European MSA Study Group, Innsbruck Medical University, Austria</affiliation>
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<author><persName><forename type="first">Manja</forename>
<surname>Kloss</surname>
<roleName type="degree">MD</roleName>
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<affiliation>Department of Neurology, University of Heidelberg, Germany</affiliation>
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<author><persName><forename type="first">Martin</forename>
<surname>Krause</surname>
<roleName type="degree">MD</roleName>
</persName>
<affiliation>Department of Neurology, University of Heidelberg, Germany</affiliation>
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<author><persName><forename type="first">Christine</forename>
<surname>Daniels</surname>
<roleName type="degree">MD</roleName>
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<affiliation>Department of Neurology, University of Kiel, Germany</affiliation>
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<author><persName><forename type="first">Günther</forename>
<surname>Deuschl</surname>
<roleName type="degree">MD</roleName>
</persName>
<affiliation>Department of Neurology, University of Kiel, Germany</affiliation>
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<author><persName><forename type="first">Silke</forename>
<surname>Böttger</surname>
<roleName type="degree">MD</roleName>
</persName>
<affiliation>Department of Neurology, University of Würzburg, Germany</affiliation>
</author>
<author><persName><forename type="first">Markus</forename>
<surname>Naumann</surname>
<roleName type="degree">MD</roleName>
</persName>
<affiliation>Department of Neurology, University of Würzburg, Germany</affiliation>
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<author><persName><forename type="first">Axel</forename>
<surname>Lipp</surname>
<roleName type="degree">MD</roleName>
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<affiliation>Wolfson Molecular Imaging Centre, The University of Manchester, United Kingdom</affiliation>
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<author><persName><forename type="first">Doreen</forename>
<surname>Gruber</surname>
<roleName type="degree">MD</roleName>
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<affiliation>Department of Neurology, University of Berlin, Germany</affiliation>
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<author><persName><forename type="first">Andreas</forename>
<surname>Kupsch</surname>
<roleName type="degree">MD, PhD</roleName>
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<affiliation>Department of Neurology, University of Berlin, Germany</affiliation>
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<author><persName><forename type="first">Yansheng</forename>
<surname>Du</surname>
<roleName type="degree">PhD</roleName>
</persName>
<affiliation>Department of Neurology, Indiana University Medical School, Indianapolis, Indiana, USA</affiliation>
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<author><persName><forename type="first">Federico</forename>
<surname>Turkheimer</surname>
<roleName type="degree">PhD</roleName>
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<affiliation>IMRC Clinical Sciences Centre and Division of Neuroscience, Faculty of Medicine, Imperial College; London, United Kingdom</affiliation>
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<author><persName><forename type="first">David J.</forename>
<surname>Brooks</surname>
<roleName type="degree">MD</roleName>
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<affiliation>IMRC Clinical Sciences Centre and Division of Neuroscience, Faculty of Medicine, Imperial College; London, United Kingdom</affiliation>
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<author><persName><forename type="first">Thomas</forename>
<surname>Klockgether</surname>
<roleName type="degree">MD</roleName>
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<affiliation>Department of Neurology, University of Bonn, Germany</affiliation>
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<author><persName><forename type="first">Werner</forename>
<surname>Poewe</surname>
<roleName type="degree">MD</roleName>
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<affiliation>Department of Neurology, Medical University of Innsbruck, Austria</affiliation>
<affiliation>European MSA Study Group, Innsbruck Medical University, Austria</affiliation>
</author>
<author><persName><forename type="first">Gregor</forename>
<surname>Wenning</surname>
<roleName type="degree">MD, PhD</roleName>
</persName>
<affiliation>Department of Neurology, Medical University of Innsbruck, Austria</affiliation>
<affiliation>European MSA Study Group, Innsbruck Medical University, Austria</affiliation>
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<author><persName><forename type="first">Carmen</forename>
<surname>Schade‐Brittinger</surname>
<roleName type="degree">, MSc</roleName>
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<affiliation>Coordinating Center for Clinical Trials, Philipps‐University of Marburg, Germany</affiliation>
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<author><persName><forename type="first">Wolfgang H.</forename>
<surname>Oertel</surname>
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<abstract xml:lang="en"><p>The aim of the study was to investigate the efficacy of the antibiotic minocycline as a drug treatment in patients with Multiple‐System‐Atrophy Parkinson‐type (MSA‐P). Sixty‐three patients were randomized to minocycline 200 mg/d (n = 32) or a matching placebo (n = 31). The primary outcome variable was the change in the value of the motor score of the Unified Multiple‐System‐Atrophy Rating‐Scale (UMSARSII) from baseline to 48 weeks. Secondary outcome variables included subscores and individual Parkinsonian symptoms as determined by the UMSARS and the Unified‐Parkinson's‐Disease Rating‐Scale (UPDRS). Health‐related quality of life (HrQoL) was assessed using the EQ‐5D and SF‐12. “Progression rate” was assumed to be reflected in the change in motor function over 48 weeks. At 24 weeks and 48 weeks of follow‐up, there was a significant deterioration in motor scores in both groups, but neither the change in UMSARSII nor in UPDRSIII differed significantly between treatment groups, i.e. “progression rate” was considered to be similar in both treatment arms. HrQoL did not differ among the two treatment arms. In a small subgroup of patients (n = 8; minocycline = 3, placebo = 5)[11C](R)‐PK11195‐PET was performed. The three patients in the minocycline group had an attenuated mean increase in microglial activation as compared to the placebo group (P = 0.07) and in two of them individually showed decreased [11C](R)‐PK11195 binding actually decreased. These preliminary PET‐data suggest that minocycline may interfere with microglial activation. The relevance of this observation requires further investigation. This prospective, 48 week, randomized, double‐blind, multinational study failed to show a clinical effect of minocycline on symptom severity as assessed by clinical motor function. © 2009 Movement Disorder Society</p>
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<p>The aim of the study was to investigate the efficacy of the antibiotic minocycline as a drug treatment in patients with Multiple‐System‐Atrophy Parkinson‐type (MSA‐P). Sixty‐three patients were randomized to minocycline 200 mg/d (n = 32) or a matching placebo (n = 31). The primary outcome variable was the change in the value of the motor score of the Unified Multiple‐System‐Atrophy Rating‐Scale (UMSARSII) from baseline to 48 weeks. Secondary outcome variables included subscores and individual Parkinsonian symptoms as determined by the UMSARS and the Unified‐Parkinson's‐Disease Rating‐Scale (UPDRS). Health‐related quality of life (HrQoL) was assessed using the EQ‐5D and SF‐12. “Progression rate” was assumed to be reflected in the change in motor function over 48 weeks. At 24 weeks and 48 weeks of follow‐up, there was a significant deterioration in motor scores in both groups, but neither the change in UMSARSII nor in UPDRSIII differed significantly between treatment groups, i.e. “progression rate” was considered to be similar in both treatment arms. HrQoL did not differ among the two treatment arms. In a small subgroup of patients (n = 8; minocycline = 3, placebo = 5)[<sup>11</sup>
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<noteGroup><note xml:id="fn5"><p>Potential conflict of interest: The authors report no conflicts of interest and have no financial disclosures to make in respect to this article.</p>
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<note xml:id="fn6"><p>Richard Dodel, Annika Spottke, Alexander Gerhard, Alexander Reuss, Wolfgang H. Oertel, and Karla Eggert contributed equally to this work.</p>
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<affiliation>Paracelsus‐Elena‐Clinic Kassel, Germany</affiliation>
<role><roleTerm type="text">author</roleTerm>
</role>
</name>
<name type="personal"><namePart type="given">Birgit</namePart>
<namePart type="family">Herting</namePart>
<namePart type="termsOfAddress">MD</namePart>
<affiliation>Department of Neurology, Dresden University of Technology, Germany</affiliation>
<role><roleTerm type="text">author</roleTerm>
</role>
</name>
<name type="personal"><namePart type="given">Christoph</namePart>
<namePart type="family">Kamm</namePart>
<namePart type="termsOfAddress">MD</namePart>
<affiliation>Hertie‐Institute, University of Tübingen, Germany</affiliation>
<affiliation>Department of Neurology, University of Rostock, Germany</affiliation>
<role><roleTerm type="text">author</roleTerm>
</role>
</name>
<name type="personal"><namePart type="given">Thomas</namePart>
<namePart type="family">Gasser</namePart>
<namePart type="termsOfAddress">MD</namePart>
<affiliation>Hertie‐Institute, University of Tübingen, Germany</affiliation>
<role><roleTerm type="text">author</roleTerm>
</role>
</name>
<name type="personal"><namePart type="given">Martin</namePart>
<namePart type="family">Sawires</namePart>
<namePart type="termsOfAddress">MD</namePart>
<affiliation>Department of Neurology, Medical University of Innsbruck, Austria</affiliation>
<role><roleTerm type="text">author</roleTerm>
</role>
</name>
<name type="personal"><namePart type="given">Felix</namePart>
<namePart type="family">Geser</namePart>
<namePart type="termsOfAddress">MD, PhD</namePart>
<affiliation>Department of Neurology, Medical University of Innsbruck, Austria</affiliation>
<affiliation>European MSA Study Group, Innsbruck Medical University, Austria</affiliation>
<role><roleTerm type="text">author</roleTerm>
</role>
</name>
<name type="personal"><namePart type="given">Martin</namePart>
<namePart type="family">Köllensperger</namePart>
<namePart type="termsOfAddress">MD</namePart>
<affiliation>Department of Neurology, Medical University of Innsbruck, Austria</affiliation>
<role><roleTerm type="text">author</roleTerm>
</role>
</name>
<name type="personal"><namePart type="given">Klaus</namePart>
<namePart type="family">Seppi</namePart>
<namePart type="termsOfAddress">MD</namePart>
<affiliation>Department of Neurology, Medical University of Innsbruck, Austria</affiliation>
<affiliation>European MSA Study Group, Innsbruck Medical University, Austria</affiliation>
<role><roleTerm type="text">author</roleTerm>
</role>
</name>
<name type="personal"><namePart type="given">Manja</namePart>
<namePart type="family">Kloss</namePart>
<namePart type="termsOfAddress">MD</namePart>
<affiliation>Department of Neurology, University of Heidelberg, Germany</affiliation>
<role><roleTerm type="text">author</roleTerm>
</role>
</name>
<name type="personal"><namePart type="given">Martin</namePart>
<namePart type="family">Krause</namePart>
<namePart type="termsOfAddress">MD</namePart>
<affiliation>Department of Neurology, University of Heidelberg, Germany</affiliation>
<role><roleTerm type="text">author</roleTerm>
</role>
</name>
<name type="personal"><namePart type="given">Christine</namePart>
<namePart type="family">Daniels</namePart>
<namePart type="termsOfAddress">MD</namePart>
<affiliation>Department of Neurology, University of Kiel, Germany</affiliation>
<role><roleTerm type="text">author</roleTerm>
</role>
</name>
<name type="personal"><namePart type="given">Günther</namePart>
<namePart type="family">Deuschl</namePart>
<namePart type="termsOfAddress">MD</namePart>
<affiliation>Department of Neurology, University of Kiel, Germany</affiliation>
<role><roleTerm type="text">author</roleTerm>
</role>
</name>
<name type="personal"><namePart type="given">Silke</namePart>
<namePart type="family">Böttger</namePart>
<namePart type="termsOfAddress">MD</namePart>
<affiliation>Department of Neurology, University of Würzburg, Germany</affiliation>
<role><roleTerm type="text">author</roleTerm>
</role>
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<name type="personal"><namePart type="given">Markus</namePart>
<namePart type="family">Naumann</namePart>
<namePart type="termsOfAddress">MD</namePart>
<affiliation>Department of Neurology, University of Würzburg, Germany</affiliation>
<role><roleTerm type="text">author</roleTerm>
</role>
</name>
<name type="personal"><namePart type="given">Axel</namePart>
<namePart type="family">Lipp</namePart>
<namePart type="termsOfAddress">MD</namePart>
<affiliation>Wolfson Molecular Imaging Centre, The University of Manchester, United Kingdom</affiliation>
<role><roleTerm type="text">author</roleTerm>
</role>
</name>
<name type="personal"><namePart type="given">Doreen</namePart>
<namePart type="family">Gruber</namePart>
<namePart type="termsOfAddress">MD</namePart>
<affiliation>Department of Neurology, University of Berlin, Germany</affiliation>
<role><roleTerm type="text">author</roleTerm>
</role>
</name>
<name type="personal"><namePart type="given">Andreas</namePart>
<namePart type="family">Kupsch</namePart>
<namePart type="termsOfAddress">MD, PhD</namePart>
<affiliation>Department of Neurology, University of Berlin, Germany</affiliation>
<role><roleTerm type="text">author</roleTerm>
</role>
</name>
<name type="personal"><namePart type="given">Yansheng</namePart>
<namePart type="family">Du</namePart>
<namePart type="termsOfAddress">PhD</namePart>
<affiliation>Department of Neurology, Indiana University Medical School, Indianapolis, Indiana, USA</affiliation>
<role><roleTerm type="text">author</roleTerm>
</role>
</name>
<name type="personal"><namePart type="given">Federico</namePart>
<namePart type="family">Turkheimer</namePart>
<namePart type="termsOfAddress">PhD</namePart>
<affiliation>IMRC Clinical Sciences Centre and Division of Neuroscience, Faculty of Medicine, Imperial College; London, United Kingdom</affiliation>
<role><roleTerm type="text">author</roleTerm>
</role>
</name>
<name type="personal"><namePart type="given">David J.</namePart>
<namePart type="family">Brooks</namePart>
<namePart type="termsOfAddress">MD</namePart>
<affiliation>IMRC Clinical Sciences Centre and Division of Neuroscience, Faculty of Medicine, Imperial College; London, United Kingdom</affiliation>
<role><roleTerm type="text">author</roleTerm>
</role>
</name>
<name type="personal"><namePart type="given">Thomas</namePart>
<namePart type="family">Klockgether</namePart>
<namePart type="termsOfAddress">MD</namePart>
<affiliation>Department of Neurology, University of Bonn, Germany</affiliation>
<role><roleTerm type="text">author</roleTerm>
</role>
</name>
<name type="personal"><namePart type="given">Werner</namePart>
<namePart type="family">Poewe</namePart>
<namePart type="termsOfAddress">MD</namePart>
<affiliation>Department of Neurology, Medical University of Innsbruck, Austria</affiliation>
<affiliation>European MSA Study Group, Innsbruck Medical University, Austria</affiliation>
<role><roleTerm type="text">author</roleTerm>
</role>
</name>
<name type="personal"><namePart type="given">Gregor</namePart>
<namePart type="family">Wenning</namePart>
<namePart type="termsOfAddress">MD, PhD</namePart>
<affiliation>Department of Neurology, Medical University of Innsbruck, Austria</affiliation>
<affiliation>European MSA Study Group, Innsbruck Medical University, Austria</affiliation>
<role><roleTerm type="text">author</roleTerm>
</role>
</name>
<name type="personal"><namePart type="given">Carmen</namePart>
<namePart type="family">Schade‐Brittinger</namePart>
<namePart type="termsOfAddress">, MSc</namePart>
<affiliation>Coordinating Center for Clinical Trials, Philipps‐University of Marburg, Germany</affiliation>
<role><roleTerm type="text">author</roleTerm>
</role>
</name>
<name type="personal"><namePart type="given">Wolfgang H.</namePart>
<namePart type="family">Oertel</namePart>
<namePart type="termsOfAddress">MD</namePart>
<affiliation>Department of Neurology, Philipps‐University of Marburg, Germany</affiliation>
<affiliation>Competence Network Parkinson‐Syndrome, Philipps‐University of Marburg, Germany</affiliation>
<description>Richard Dodel, Annika Spottke, Alexander Gerhard, Alexander Reuss, Wolfgang H. Oertel, and Karla Eggert contributed equally to this work.</description>
<role><roleTerm type="text">author</roleTerm>
</role>
</name>
<name type="personal"><namePart type="given">Karla</namePart>
<namePart type="family">Eggert</namePart>
<namePart type="termsOfAddress">MD</namePart>
<affiliation>Department of Neurology, Philipps‐University of Marburg, Germany</affiliation>
<affiliation>Competence Network Parkinson‐Syndrome, Philipps‐University of Marburg, Germany</affiliation>
<description>Richard Dodel, Annika Spottke, Alexander Gerhard, Alexander Reuss, Wolfgang H. Oertel, and Karla Eggert contributed equally to this work.</description>
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<dateIssued encoding="w3cdtf">2010-01-15</dateIssued>
<dateCaptured encoding="w3cdtf">2008-01-23</dateCaptured>
<dateValid encoding="w3cdtf">2009-07-08</dateValid>
<copyrightDate encoding="w3cdtf">2010</copyrightDate>
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<abstract lang="en">The aim of the study was to investigate the efficacy of the antibiotic minocycline as a drug treatment in patients with Multiple‐System‐Atrophy Parkinson‐type (MSA‐P). Sixty‐three patients were randomized to minocycline 200 mg/d (n = 32) or a matching placebo (n = 31). The primary outcome variable was the change in the value of the motor score of the Unified Multiple‐System‐Atrophy Rating‐Scale (UMSARSII) from baseline to 48 weeks. Secondary outcome variables included subscores and individual Parkinsonian symptoms as determined by the UMSARS and the Unified‐Parkinson's‐Disease Rating‐Scale (UPDRS). Health‐related quality of life (HrQoL) was assessed using the EQ‐5D and SF‐12. “Progression rate” was assumed to be reflected in the change in motor function over 48 weeks. At 24 weeks and 48 weeks of follow‐up, there was a significant deterioration in motor scores in both groups, but neither the change in UMSARSII nor in UPDRSIII differed significantly between treatment groups, i.e. “progression rate” was considered to be similar in both treatment arms. HrQoL did not differ among the two treatment arms. In a small subgroup of patients (n = 8; minocycline = 3, placebo = 5)[11C](R)‐PK11195‐PET was performed. The three patients in the minocycline group had an attenuated mean increase in microglial activation as compared to the placebo group (P = 0.07) and in two of them individually showed decreased [11C](R)‐PK11195 binding actually decreased. These preliminary PET‐data suggest that minocycline may interfere with microglial activation. The relevance of this observation requires further investigation. This prospective, 48 week, randomized, double‐blind, multinational study failed to show a clinical effect of minocycline on symptom severity as assessed by clinical motor function. © 2009 Movement Disorder Society</abstract>
<note type="content">*Potential conflict of interest: The authors report no conflicts of interest and have no financial disclosures to make in respect to this article.</note>
<note type="funding">German Ministry of Education and Research - No. BMBF Nr. 01GI9901; No. 01GI0201; No. 01GI040; </note>
<note type="funding">European MSA Study Group</note>
<note type="funding">Willy Robert Pitzer foundation - No. 16/03; No. PDS UK MAP; No. 02/04; </note>
<subject lang="en"><genre>Keywords</genre>
<topic>multiple system atrophy</topic>
<topic>minocycline</topic>
<topic>PET</topic>
</subject>
<relatedItem type="host"><titleInfo><title>Movement Disorders</title>
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<titleInfo type="abbreviated"><title>Mov. Disord.</title>
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<topic>Research Article</topic>
</subject>
<identifier type="ISSN">0885-3185</identifier>
<identifier type="eISSN">1531-8257</identifier>
<identifier type="DOI">10.1002/(ISSN)1531-8257</identifier>
<identifier type="PublisherID">MDS</identifier>
<part><date>2010</date>
<detail type="volume"><caption>vol.</caption>
<number>25</number>
</detail>
<detail type="issue"><caption>no.</caption>
<number>1</number>
</detail>
<extent unit="pages"><start>97</start>
<end>107</end>
<total>11</total>
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</part>
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<identifier type="DOI">10.1002/mds.22732</identifier>
<identifier type="ArticleID">MDS22732</identifier>
<accessCondition type="use and reproduction" contentType="copyright">Copyright © 2009 Movement Disorder Society</accessCondition>
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