Priorities in Parkinson's disease research
Identifieur interne : 000002 ( Main/Corpus ); précédent : 000001; suivant : 000003Priorities in Parkinson's disease research
Auteurs : Wassilios G. Meissner ; Mark Frasier ; Thomas Gasser ; Christopher G. Goetz ; Andres Lozano ; Paola Piccini ; José A. Obeso ; Olivier Rascol ; Anthony Schapira ; Valerie Voon ; David M. Weiner ; François Tison ; Erwan BezardSource :
- Nature Reviews Drug Discovery [ 1474-1776 ] ; 2011-05.
Abstract
The loss of dopaminergic neurons in the substantia nigra pars compacta leads to the characteristic motor symptoms of Parkinson's disease: bradykinesia, rigidity and resting tremors. Although these symptoms can be improved using currently available dopamine replacement strategies, there is still a need to improve current strategies of treating these symptoms, together with a need to alleviate non-motor symptoms of the disease. Moreover, treatments that provide neuroprotection and/or disease-modifying effects remain an urgent unmet clinical need. This Review describes the most promising biological targets and therapeutic agents that are currently being assessed to address these treatment goals. Progress will rely on understanding genetic mutations or susceptibility factors that lead to Parkinson's disease, better translation between preclinical animal models and clinical research, and improving the design of future clinical trials.>
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DOI: 10.1038/nrd3430
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Meissner</name><affiliation><mods:affiliation>Service de Neurologie et Centre de référence atrophie multisystématisée, CHU de Bordeaux, Avenue Magellan F-33604 Pessac France.</mods:affiliation></affiliation><affiliation><mods:affiliation>Université de Bordeaux, Institut des Maladies Neurodégénératives, UMR 5293, F-33000 Bordeaux, France.</mods:affiliation></affiliation><affiliation><mods:affiliation>CNRS, Institut des Maladies Neurodégénératives, UMR 5293, F-33000 Bordeaux, France.</mods:affiliation></affiliation><affiliation><mods:affiliation>E-mail: wassilios.meissner@chu-bordeaux.fr</mods:affiliation></affiliation></author><author><name sortKey="Frasier, Mark" sort="Frasier, Mark" uniqKey="Frasier M" first="Mark" last="Frasier">Mark Frasier</name><affiliation><mods:affiliation>Michael J. Fox Foundation for Parkinson's Research, New York, New York 10004, USA.</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>Department of Neurodegenerative Diseases, Hertie Institute for Clinical Brain Research, University of Tübingen and DZNE — German Center for Neurodegenerative Diseases, D-72076 Tübingen, Germany.</mods:affiliation></affiliation></author><author><name sortKey="Goetz, Christopher G" sort="Goetz, Christopher G" uniqKey="Goetz C" first="Christopher G." last="Goetz">Christopher G. Goetz</name><affiliation><mods:affiliation>Department of Neurological Sciences, Rush University Medical Center, Chicago, Illinois 60612, USA.</mods:affiliation></affiliation></author><author><name sortKey="Lozano, Andres" sort="Lozano, Andres" uniqKey="Lozano A" first="Andres" last="Lozano">Andres Lozano</name><affiliation><mods:affiliation>Department of Neurosurgery, Toronto Western Hospital, University of Toronto, Toronto, Ontario M5T 2S8, Canada.</mods:affiliation></affiliation></author><author><name sortKey="Piccini, Paola" sort="Piccini, Paola" uniqKey="Piccini P" first="Paola" last="Piccini">Paola Piccini</name><affiliation><mods:affiliation>Centre for Neuroscience, Imperial College London, London, SW7 2AZ, UK.</mods:affiliation></affiliation></author><author><name sortKey="Obeso, Jose A" sort="Obeso, Jose A" uniqKey="Obeso J" first="José A." last="Obeso">José A. Obeso</name><affiliation><mods:affiliation>Movement Disorders Group, Neurosciences Division, CIMA, and Department of Neurology and Neurosurgery, Clínica Universitaria and CIBERNED, University of Navarra, 31008 Pamplona, Spain.</mods:affiliation></affiliation></author><author><name sortKey="Rascol, Olivier" sort="Rascol, Olivier" uniqKey="Rascol O" first="Olivier" last="Rascol">Olivier Rascol</name><affiliation><mods:affiliation>Departments of Clinical Pharmacology and Neurosciences, INSERM CIC9302, University Hospital of Toulouse, 31000 Toulouse, France.</mods:affiliation></affiliation></author><author><name sortKey="Schapira, Anthony" sort="Schapira, Anthony" uniqKey="Schapira A" first="Anthony" last="Schapira">Anthony Schapira</name><affiliation><mods:affiliation>Department of Clinical Neurosciences, Institute of Neurology, University College London, London NW3 2PF, UK.</mods:affiliation></affiliation></author><author><name sortKey="Voon, Valerie" sort="Voon, Valerie" uniqKey="Voon V" first="Valerie" last="Voon">Valerie Voon</name><affiliation><mods:affiliation>Behavioral and Clinical Neurosciences Institute, University of Cambridge, Cambridge CB2 0SZ, UK.</mods:affiliation></affiliation></author><author><name sortKey="Weiner, David M" sort="Weiner, David M" uniqKey="Weiner D" first="David M." last="Weiner">David M. Weiner</name><affiliation><mods:affiliation>EMD Serono, Rockland, Massachusetts 02370, USA.</mods:affiliation></affiliation></author><author><name sortKey="Tison, Francois" sort="Tison, Francois" uniqKey="Tison F" first="François" last="Tison">François Tison</name><affiliation><mods:affiliation>Service de Neurologie et Centre de référence atrophie multisystématisée, CHU de Bordeaux, Avenue Magellan F-33604 Pessac France.</mods:affiliation></affiliation><affiliation><mods:affiliation>Université de Bordeaux, Institut des Maladies Neurodégénératives, UMR 5293, F-33000 Bordeaux, France.</mods:affiliation></affiliation><affiliation><mods:affiliation>CNRS, Institut des Maladies Neurodégénératives, UMR 5293, F-33000 Bordeaux, France.</mods:affiliation></affiliation></author><author><name sortKey="Bezard, Erwan" sort="Bezard, Erwan" uniqKey="Bezard E" first="Erwan" last="Bezard">Erwan Bezard</name><affiliation><mods:affiliation>Service de Neurologie et Centre de référence atrophie multisystématisée, CHU de Bordeaux, Avenue Magellan F-33604 Pessac France.</mods:affiliation></affiliation><affiliation><mods:affiliation>CNRS, Institut des Maladies Neurodégénératives, UMR 5293, F-33000 Bordeaux, France.</mods:affiliation></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">ISTEX</idno><idno type="RBID">ISTEX:B18DB94A38D88A12D621F99E69D4EEFEBBE7059E</idno><date when="2011" year="2011">2011</date><idno type="doi">10.1038/nrd3430</idno><idno type="url">https://api.istex.fr/document/B18DB94A38D88A12D621F99E69D4EEFEBBE7059E/fulltext/pdf</idno><idno type="wicri:Area/Main/Corpus">000002</idno></publicationStmt><sourceDesc><biblStruct><analytic><title level="a" type="main" xml:lang="en">Priorities in Parkinson's disease research</title><author><name sortKey="Meissner, Wassilios G" sort="Meissner, Wassilios G" uniqKey="Meissner W" first="Wassilios G." last="Meissner">Wassilios G. Meissner</name><affiliation><mods:affiliation>Service de Neurologie et Centre de référence atrophie multisystématisée, CHU de Bordeaux, Avenue Magellan F-33604 Pessac France.</mods:affiliation></affiliation><affiliation><mods:affiliation>Université de Bordeaux, Institut des Maladies Neurodégénératives, UMR 5293, F-33000 Bordeaux, France.</mods:affiliation></affiliation><affiliation><mods:affiliation>CNRS, Institut des Maladies Neurodégénératives, UMR 5293, F-33000 Bordeaux, France.</mods:affiliation></affiliation><affiliation><mods:affiliation>E-mail: wassilios.meissner@chu-bordeaux.fr</mods:affiliation></affiliation></author><author><name sortKey="Frasier, Mark" sort="Frasier, Mark" uniqKey="Frasier M" first="Mark" last="Frasier">Mark Frasier</name><affiliation><mods:affiliation>Michael J. Fox Foundation for Parkinson's Research, New York, New York 10004, USA.</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>Department of Neurodegenerative Diseases, Hertie Institute for Clinical Brain Research, University of Tübingen and DZNE — German Center for Neurodegenerative Diseases, D-72076 Tübingen, Germany.</mods:affiliation></affiliation></author><author><name sortKey="Goetz, Christopher G" sort="Goetz, Christopher G" uniqKey="Goetz C" first="Christopher G." last="Goetz">Christopher G. Goetz</name><affiliation><mods:affiliation>Department of Neurological Sciences, Rush University Medical Center, Chicago, Illinois 60612, USA.</mods:affiliation></affiliation></author><author><name sortKey="Lozano, Andres" sort="Lozano, Andres" uniqKey="Lozano A" first="Andres" last="Lozano">Andres Lozano</name><affiliation><mods:affiliation>Department of Neurosurgery, Toronto Western Hospital, University of Toronto, Toronto, Ontario M5T 2S8, Canada.</mods:affiliation></affiliation></author><author><name sortKey="Piccini, Paola" sort="Piccini, Paola" uniqKey="Piccini P" first="Paola" last="Piccini">Paola Piccini</name><affiliation><mods:affiliation>Centre for Neuroscience, Imperial College London, London, SW7 2AZ, UK.</mods:affiliation></affiliation></author><author><name sortKey="Obeso, Jose A" sort="Obeso, Jose A" uniqKey="Obeso J" first="José A." last="Obeso">José A. Obeso</name><affiliation><mods:affiliation>Movement Disorders Group, Neurosciences Division, CIMA, and Department of Neurology and Neurosurgery, Clínica Universitaria and CIBERNED, University of Navarra, 31008 Pamplona, Spain.</mods:affiliation></affiliation></author><author><name sortKey="Rascol, Olivier" sort="Rascol, Olivier" uniqKey="Rascol O" first="Olivier" last="Rascol">Olivier Rascol</name><affiliation><mods:affiliation>Departments of Clinical Pharmacology and Neurosciences, INSERM CIC9302, University Hospital of Toulouse, 31000 Toulouse, France.</mods:affiliation></affiliation></author><author><name sortKey="Schapira, Anthony" sort="Schapira, Anthony" uniqKey="Schapira A" first="Anthony" last="Schapira">Anthony Schapira</name><affiliation><mods:affiliation>Department of Clinical Neurosciences, Institute of Neurology, University College London, London NW3 2PF, UK.</mods:affiliation></affiliation></author><author><name sortKey="Voon, Valerie" sort="Voon, Valerie" uniqKey="Voon V" first="Valerie" last="Voon">Valerie Voon</name><affiliation><mods:affiliation>Behavioral and Clinical Neurosciences Institute, University of Cambridge, Cambridge CB2 0SZ, UK.</mods:affiliation></affiliation></author><author><name sortKey="Weiner, David M" sort="Weiner, David M" uniqKey="Weiner D" first="David M." last="Weiner">David M. Weiner</name><affiliation><mods:affiliation>EMD Serono, Rockland, Massachusetts 02370, USA.</mods:affiliation></affiliation></author><author><name sortKey="Tison, Francois" sort="Tison, Francois" uniqKey="Tison F" first="François" last="Tison">François Tison</name><affiliation><mods:affiliation>Service de Neurologie et Centre de référence atrophie multisystématisée, CHU de Bordeaux, Avenue Magellan F-33604 Pessac France.</mods:affiliation></affiliation><affiliation><mods:affiliation>Université de Bordeaux, Institut des Maladies Neurodégénératives, UMR 5293, F-33000 Bordeaux, France.</mods:affiliation></affiliation><affiliation><mods:affiliation>CNRS, Institut des Maladies Neurodégénératives, UMR 5293, F-33000 Bordeaux, France.</mods:affiliation></affiliation></author><author><name sortKey="Bezard, Erwan" sort="Bezard, Erwan" uniqKey="Bezard E" first="Erwan" last="Bezard">Erwan Bezard</name><affiliation><mods:affiliation>Service de Neurologie et Centre de référence atrophie multisystématisée, CHU de Bordeaux, Avenue Magellan F-33604 Pessac France.</mods:affiliation></affiliation><affiliation><mods:affiliation>CNRS, Institut des Maladies Neurodégénératives, UMR 5293, F-33000 Bordeaux, France.</mods:affiliation></affiliation></author></analytic><monogr></monogr><series><title level="j">Nature Reviews Drug Discovery</title><idno type="ISSN">1474-1776</idno><idno type="eISSN">1474-1784</idno><imprint><publisher>Nature Publishing Group, a division of Macmillan Publishers Limited. All Rights Reserved.</publisher><date type="published" when="2011-05">2011-05</date><biblScope unit="volume">10</biblScope><biblScope unit="issue">5</biblScope><biblScope unit="page" from="377">377</biblScope><biblScope unit="page" to="393">393</biblScope></imprint><idno type="ISSN">1474-1776</idno></series><idno type="istex">B18DB94A38D88A12D621F99E69D4EEFEBBE7059E</idno><idno type="DOI">10.1038/nrd3430</idno><idno type="ArticleID">nrd3430</idno></biblStruct></sourceDesc><seriesStmt><idno type="ISSN">1474-1776</idno></seriesStmt></fileDesc><profileDesc><textClass></textClass><langUsage><language ident="en">en</language></langUsage></profileDesc></teiHeader><front><div type="abstract" xml:lang="eng">The loss of dopaminergic neurons in the substantia nigra pars compacta leads to the characteristic motor symptoms of Parkinson's disease: bradykinesia, rigidity and resting tremors. Although these symptoms can be improved using currently available dopamine replacement strategies, there is still a need to improve current strategies of treating these symptoms, together with a need to alleviate non-motor symptoms of the disease. Moreover, treatments that provide neuroprotection and/or disease-modifying effects remain an urgent unmet clinical need. This Review describes the most promising biological targets and therapeutic agents that are currently being assessed to address these treatment goals. Progress will rely on understanding genetic mutations or susceptibility factors that lead to Parkinson's disease, better translation between preclinical animal models and clinical research, and improving the design of future clinical trials.></div></front></TEI><istex><corpusName>nature</corpusName><author><json:item><name>Wassilios G. Meissner</name><affiliations><json:string>Service de Neurologie et Centre de référence atrophie multisystématisée, CHU de Bordeaux, Avenue Magellan F-33604 Pessac France.</json:string><json:string>Université de Bordeaux, Institut des Maladies Neurodégénératives, UMR 5293, F-33000 Bordeaux, France.</json:string><json:string>CNRS, Institut des Maladies Neurodégénératives, UMR 5293, F-33000 Bordeaux, France.</json:string><json:string>E-mail: wassilios.meissner@chu-bordeaux.fr</json:string></affiliations></json:item><json:item><name>Mark Frasier</name><affiliations><json:string>Michael J. Fox Foundation for Parkinson's Research, New York, New York 10004, USA.</json:string></affiliations></json:item><json:item><name>Thomas Gasser</name><affiliations><json:string>Department of Neurodegenerative Diseases, Hertie Institute for Clinical Brain Research, University of Tübingen and DZNE — German Center for Neurodegenerative Diseases, D-72076 Tübingen, Germany.</json:string></affiliations></json:item><json:item><name>Christopher G. Goetz</name><affiliations><json:string>Department of Neurological Sciences, Rush University Medical Center, Chicago, Illinois 60612, USA.</json:string></affiliations></json:item><json:item><name>Andres Lozano</name><affiliations><json:string>Department of Neurosurgery, Toronto Western Hospital, University of Toronto, Toronto, Ontario M5T 2S8, Canada.</json:string></affiliations></json:item><json:item><name>Paola Piccini</name><affiliations><json:string>Centre for Neuroscience, Imperial College London, London, SW7 2AZ, UK.</json:string></affiliations></json:item><json:item><name>José A. Obeso</name><affiliations><json:string>Movement Disorders Group, Neurosciences Division, CIMA, and Department of Neurology and Neurosurgery, Clínica Universitaria and CIBERNED, University of Navarra, 31008 Pamplona, Spain.</json:string></affiliations></json:item><json:item><name>Olivier Rascol</name><affiliations><json:string>Departments of Clinical Pharmacology and Neurosciences, INSERM CIC9302, University Hospital of Toulouse, 31000 Toulouse, France.</json:string></affiliations></json:item><json:item><name>Anthony Schapira</name><affiliations><json:string>Department of Clinical Neurosciences, Institute of Neurology, University College London, London NW3 2PF, UK.</json:string></affiliations></json:item><json:item><name>Valerie Voon</name><affiliations><json:string>Behavioral and Clinical Neurosciences Institute, University of Cambridge, Cambridge CB2 0SZ, UK.</json:string></affiliations></json:item><json:item><name>David M. Weiner</name><affiliations><json:string>EMD Serono, Rockland, Massachusetts 02370, USA.</json:string></affiliations></json:item><json:item><name>François Tison</name><affiliations><json:string>Service de Neurologie et Centre de référence atrophie multisystématisée, CHU de Bordeaux, Avenue Magellan F-33604 Pessac France.</json:string><json:string>Université de Bordeaux, Institut des Maladies Neurodégénératives, UMR 5293, F-33000 Bordeaux, France.</json:string><json:string>CNRS, Institut des Maladies Neurodégénératives, UMR 5293, F-33000 Bordeaux, France.</json:string></affiliations></json:item><json:item><name>Erwan Bezard</name><affiliations><json:string>Service de Neurologie et Centre de référence atrophie multisystématisée, CHU de Bordeaux, Avenue Magellan F-33604 Pessac France.</json:string><json:string>CNRS, Institut des Maladies Neurodégénératives, UMR 5293, F-33000 Bordeaux, France.</json:string></affiliations></json:item></author><language><json:string>eng</json:string></language><abstract>The loss of dopaminergic neurons in the substantia nigra pars compacta leads to the characteristic motor symptoms of Parkinson's disease: bradykinesia, rigidity and resting tremors. Although these symptoms can be improved using currently available dopamine replacement strategies, there is still a need to improve current strategies of treating these symptoms, together with a need to alleviate non-motor symptoms of the disease. Moreover, treatments that provide neuroprotection and/or disease-modifying effects remain an urgent unmet clinical need. This Review describes the most promising biological targets and therapeutic agents that are currently being assessed to address these treatment goals. Progress will rely on understanding genetic mutations or susceptibility factors that lead to Parkinson's disease, better translation between preclinical animal models and clinical research, and improving the design of future clinical trials.></abstract><qualityIndicators><score>8.036</score><pdfVersion>1.6</pdfVersion><pdfPageSize>595.276 x 782.362 pts</pdfPageSize><refBibsNative>true</refBibsNative><keywordCount>0</keywordCount><abstractCharCount>944</abstractCharCount><pdfWordCount>12721</pdfWordCount><pdfCharCount>90807</pdfCharCount><pdfPageCount>17</pdfPageCount><abstractWordCount>128</abstractWordCount></qualityIndicators><title>Priorities in Parkinson's disease research</title><genre><json:string>review-article</json:string></genre><host><volume>10</volume><pages><total>17</total><last>393</last><first>377</first></pages><issn><json:string>1474-1776</json:string></issn><issue>5</issue><genre></genre><language><json:string>unknown</json:string></language><eissn><json:string>1474-1784</json:string></eissn><title>Nature Reviews Drug Discovery</title></host><categories><wos><json:string>PHARMACOLOGY & PHARMACY</json:string><json:string>BIOTECHNOLOGY & APPLIED MICROBIOLOGY</json:string></wos></categories><publicationDate>2011</publicationDate><copyrightDate>2011</copyrightDate><doi><json:string>10.1038/nrd3430</json:string></doi><id>B18DB94A38D88A12D621F99E69D4EEFEBBE7059E</id><fulltext><json:item><original>true</original><mimetype>application/pdf</mimetype><extension>pdf</extension><uri>https://api.istex.fr/document/B18DB94A38D88A12D621F99E69D4EEFEBBE7059E/fulltext/pdf</uri></json:item><json:item><original>false</original><mimetype>application/zip</mimetype><extension>zip</extension><uri>https://api.istex.fr/document/B18DB94A38D88A12D621F99E69D4EEFEBBE7059E/fulltext/zip</uri></json:item><istex:fulltextTEI uri="https://api.istex.fr/document/B18DB94A38D88A12D621F99E69D4EEFEBBE7059E/fulltext/tei"><teiHeader><fileDesc><titleStmt><title level="a" type="main" xml:lang="en">Priorities in Parkinson's disease research</title></titleStmt><publicationStmt><authority>ISTEX</authority><publisher>Nature Publishing Group, a division of Macmillan Publishers Limited. All Rights Reserved.</publisher><availability><p>NATURE</p></availability><date>2011-04-29</date></publicationStmt><sourceDesc><biblStruct type="inbook"><analytic><title level="a" type="main" xml:lang="en">Priorities in Parkinson's disease research</title><author><persName><forename type="first">Wassilios G.</forename><surname>Meissner</surname></persName><email>wassilios.meissner@chu-bordeaux.fr</email><note type="biography">Wassilios G. Meissner is Associate Professor of Neurology at the University of Bordeaux, France. He is a clinical neurologist and basic neuroscientist with a specialization in Parkinson's disease (PD) and related disorders. His current research interests focus on multiple system atrophy, (biological and clinical markers of disease progression, development of disease-modifying or neuroprotective strategies), and the development of innovative techniques for deep brain stimulation in PD.</note><affiliation>Wassilios G. Meissner is Associate Professor of Neurology at the University of Bordeaux, France. He is a clinical neurologist and basic neuroscientist with a specialization in Parkinson's disease (PD) and related disorders. His current research interests focus on multiple system atrophy, (biological and clinical markers of disease progression, development of disease-modifying or neuroprotective strategies), and the development of innovative techniques for deep brain stimulation in PD.</affiliation><affiliation>Service de Neurologie et Centre de référence atrophie multisystématisée, CHU de Bordeaux, Avenue Magellan F-33604 Pessac France.</affiliation><affiliation>Université de Bordeaux, Institut des Maladies Neurodégénératives, UMR 5293, F-33000 Bordeaux, France.</affiliation><affiliation>CNRS, Institut des Maladies Neurodégénératives, UMR 5293, F-33000 Bordeaux, France.</affiliation></author><author><persName><forename type="first">Mark</forename><surname>Frasier</surname></persName><note type="biography">Mark Frasier, Ph.D, is the Director of Research Programs for the Michael J. Fox Foundation (MJFF), New York, USA. His research interests have focused on drug development in neuroscience and protein folding in neurodegeneration. His current responsibilities include managing the translational research portfolio at MJFF with a focus on biomarkers of Parkinson's disease.</note><affiliation>Mark Frasier, Ph.D, is the Director of Research Programs for the Michael J. Fox Foundation (MJFF), New York, USA. His research interests have focused on drug development in neuroscience and protein folding in neurodegeneration. His current responsibilities include managing the translational research portfolio at MJFF with a focus on biomarkers of Parkinson's disease.</affiliation><affiliation>Michael J. Fox Foundation for Parkinson's Research, New York, New York 10004, USA.</affiliation></author><author><persName><forename type="first">Thomas</forename><surname>Gasser</surname></persName><note type="biography">Thomas Gasser studied medicine at the University of Freiburg, Germany, and Yale University, New Haven, Connecticut, USA. He is Professor of Neurology and Director of the Department for Neurodegenerative Diseases at the Hertie Institute for Clinical Brain Research, Germany, and speaker of the German Center for Neurodegenerative Diseases in Tübingen (DZNE Tübingen), Germany. His research interests include genetics and the molecular basis of Parkinson's disease and other movement disorders.</note><affiliation>Thomas Gasser studied medicine at the University of Freiburg, Germany, and Yale University, New Haven, Connecticut, USA. He is Professor of Neurology and Director of the Department for Neurodegenerative Diseases at the Hertie Institute for Clinical Brain Research, Germany, and speaker of the German Center for Neurodegenerative Diseases in Tübingen (DZNE Tübingen), Germany. His research interests include genetics and the molecular basis of Parkinson's disease and other movement disorders.</affiliation><affiliation>Department of Neurodegenerative Diseases, Hertie Institute for Clinical Brain Research, University of Tübingen and DZNE — German Center for Neurodegenerative Diseases, D-72076 Tübingen, Germany.</affiliation></author><author><persName><forename type="first">Christopher G.</forename><surname>Goetz</surname></persName><note type="biography">Christopher G. Goetz is a clinical neurologist with a primary interest in Parkinson's disease and its complications, specifically dyskinesias and hallucinations. He is actively involved in the development of rating scales and testing of new scales. His research is funded by the US National Institutes of Health, the Michael J. Fox Foundation, and the Parkinson's Disease Foundation.</note><affiliation>Christopher G. Goetz is a clinical neurologist with a primary interest in Parkinson's disease and its complications, specifically dyskinesias and hallucinations. He is actively involved in the development of rating scales and testing of new scales. His research is funded by the US National Institutes of Health, the Michael J. Fox Foundation, and the Parkinson's Disease Foundation.</affiliation><affiliation>Department of Neurological Sciences, Rush University Medical Center, Chicago, Illinois 60612, USA.</affiliation></author><author><persName><forename type="first">Andres</forename><surname>Lozano</surname></persName><note type="biography">Andres Lozano is Professor and Chairman of Neurosurgery at the University of Toronto, Canada, and holds both the RR Tasker Chair in Functional Neurosurgery and a Tier 1 Canada Research Chair in Neuroscience. His laboratory is dedicated to the study of neuronal degeneration and regeneration and functional neurosurgery.</note><affiliation>Andres Lozano is Professor and Chairman of Neurosurgery at the University of Toronto, Canada, and holds both the RR Tasker Chair in Functional Neurosurgery and a Tier 1 Canada Research Chair in Neuroscience. His laboratory is dedicated to the study of neuronal degeneration and regeneration and functional neurosurgery.</affiliation><affiliation>Department of Neurosurgery, Toronto Western Hospital, University of Toronto, Toronto, Ontario M5T 2S8, Canada.</affiliation></author><author><persName><forename type="first">Paola</forename><surname>Piccini</surname></persName><note type="biography">Paola Piccini is Professor of Clinical Neurology at Imperial College London (Division of Experimental Medicine), a consultant in neurology with the Imperial College Healthcare NHS Trust and Honorary Professor at the University of Lund, Sweden. She has worked extensively in the field of movement disorders and predominantly on the use of positron emission tomography as a method of investigating the aetiology, effects and complications of therapies, particularly new neuroprotective and neurorestorative therapies in Parkinson's disease and Huntington's disease.</note><affiliation>Paola Piccini is Professor of Clinical Neurology at Imperial College London (Division of Experimental Medicine), a consultant in neurology with the Imperial College Healthcare NHS Trust and Honorary Professor at the University of Lund, Sweden. She has worked extensively in the field of movement disorders and predominantly on the use of positron emission tomography as a method of investigating the aetiology, effects and complications of therapies, particularly new neuroprotective and neurorestorative therapies in Parkinson's disease and Huntington's disease.</affiliation><affiliation>Centre for Neuroscience, Imperial College London, London, SW7 2AZ, UK.</affiliation></author><author><persName><forename type="first">José A.</forename><surname>Obeso</surname></persName><note type="biography">José A. Obeso graduated from the University of Navarra, Pamplona, Spain, in 1976 and trained in neurology and neurophysiology in San Sebastian and Pamplona, Spain. He is currently Professor of Neurology and a consultant in the Medical School and University Hospital, University of Navarra, and senior researcher at the Centre for Applied Medical Research (CIMA), at the University of Navarra. His research activity focuses on the mechanisms underlying the onset of Parkinson's disease.</note><affiliation>José A. Obeso graduated from the University of Navarra, Pamplona, Spain, in 1976 and trained in neurology and neurophysiology in San Sebastian and Pamplona, Spain. He is currently Professor of Neurology and a consultant in the Medical School and University Hospital, University of Navarra, and senior researcher at the Centre for Applied Medical Research (CIMA), at the University of Navarra. His research activity focuses on the mechanisms underlying the onset of Parkinson's disease.</affiliation><affiliation>Movement Disorders Group, Neurosciences Division, CIMA, and Department of Neurology and Neurosurgery, Clínica Universitaria and CIBERNED, University of Navarra, 31008 Pamplona, Spain.</affiliation></author><author><persName><forename type="first">Olivier</forename><surname>Rascol</surname></persName><note type="biography">Olivier Rascol M.D., Ph.D. is a neuroscientist and Professor of Clinical Pharmacology at Toulouse University Hospital, France. His main research field is Parkinson's disease (PD), clinical neuropharmacology and functional imaging, and he is actively contributing to the development of novel dopaminergic and non-dopaminergic medications for PD, including disease-modifying agents and symptomatic therapies for motor and non-motor symptoms.</note><affiliation>Olivier Rascol M.D., Ph.D. is a neuroscientist and Professor of Clinical Pharmacology at Toulouse University Hospital, France. His main research field is Parkinson's disease (PD), clinical neuropharmacology and functional imaging, and he is actively contributing to the development of novel dopaminergic and non-dopaminergic medications for PD, including disease-modifying agents and symptomatic therapies for motor and non-motor symptoms.</affiliation><affiliation>Departments of Clinical Pharmacology and Neurosciences, INSERM CIC9302, University Hospital of Toulouse, 31000 Toulouse, France.</affiliation></author><author><persName><forename type="first">Anthony</forename><surname>Schapira</surname></persName><note type="biography">Anthony Schapira, M.D., D.Sc, FRCP FMedSci, was appointed in 1990 as Chairman of the University Department of Clinical Neurosciences at the Institute of Neurology, UK, and Professor of Neurology at the National Hospital for Neurology and Neurosurgery, UK, and the Royal Free Hospital, UK. He is currently the Vice Dean of University College London Medical School, UK, and Director of the Royal Free Campus of the Medical School.</note><affiliation>Anthony Schapira, M.D., D.Sc, FRCP FMedSci, was appointed in 1990 as Chairman of the University Department of Clinical Neurosciences at the Institute of Neurology, UK, and Professor of Neurology at the National Hospital for Neurology and Neurosurgery, UK, and the Royal Free Hospital, UK. He is currently the Vice Dean of University College London Medical School, UK, and Director of the Royal Free Campus of the Medical School.</affiliation><affiliation>Department of Clinical Neurosciences, Institute of Neurology, University College London, London NW3 2PF, UK.</affiliation></author><author><persName><forename type="first">Valerie</forename><surname>Voon</surname></persName><note type="biography">Valerie Voon, M.D. Ph.D., is a neuropsychiatrist at the University of Cambridge, UK, and a Wellcome Trust Clinical Fellow. Her research focuses on mechanisms underlying impulsive and compulsive disorders in the general population and neurological disorders and utilizes cognitive paradigms, functional MRI and drug manipulation in clinical populations.</note><affiliation>Valerie Voon, M.D. Ph.D., is a neuropsychiatrist at the University of Cambridge, UK, and a Wellcome Trust Clinical Fellow. Her research focuses on mechanisms underlying impulsive and compulsive disorders in the general population and neurological disorders and utilizes cognitive paradigms, functional MRI and drug manipulation in clinical populations.</affiliation><affiliation>Behavioral and Clinical Neurosciences Institute, University of Cambridge, Cambridge CB2 0SZ, UK.</affiliation></author><author><persName><forename type="first">David M.</forename><surname>Weiner</surname></persName><note type="biography">David Weiner is a neurologist and neuropharmacologist who works on translational research in central nervous system diseases, including preclinical development efforts on compounds for schizophrenia, Parkinson's disease and sleep at Acadia Pharmaceuticals, California, USA; most recently, he led the early clinical development efforts in neurodegenerative diseases at EMD/Merck Serono.</note><affiliation>David Weiner is a neurologist and neuropharmacologist who works on translational research in central nervous system diseases, including preclinical development efforts on compounds for schizophrenia, Parkinson's disease and sleep at Acadia Pharmaceuticals, California, USA; most recently, he led the early clinical development efforts in neurodegenerative diseases at EMD/Merck Serono.</affiliation><affiliation>EMD Serono, Rockland, Massachusetts 02370, USA.</affiliation></author><author><persName><forename type="first">François</forename><surname>Tison</surname></persName><note type="biography">François Tison is Professor of Neurology at the University of Bordeaux and deputy director of the Institute of Neurodegenerative Diseases (clinical branch) in Bordeaux, France. He is head of the Parkinsonism and Movement Disorders unit and reference centre for multiple system atrophy at the University Hospital of Bordeaux, France. His main research interests in Parkinson's disease are levodopa-induced dyskinesias, epidemiology, genetics, neuropharmacology, sleep and dementia.</note><affiliation>François Tison is Professor of Neurology at the University of Bordeaux and deputy director of the Institute of Neurodegenerative Diseases (clinical branch) in Bordeaux, France. He is head of the Parkinsonism and Movement Disorders unit and reference centre for multiple system atrophy at the University Hospital of Bordeaux, France. His main research interests in Parkinson's disease are levodopa-induced dyskinesias, epidemiology, genetics, neuropharmacology, sleep and dementia.</affiliation><affiliation>Service de Neurologie et Centre de référence atrophie multisystématisée, CHU de Bordeaux, Avenue Magellan F-33604 Pessac France.</affiliation><affiliation>Université de Bordeaux, Institut des Maladies Neurodégénératives, UMR 5293, F-33000 Bordeaux, France.</affiliation><affiliation>CNRS, Institut des Maladies Neurodégénératives, UMR 5293, F-33000 Bordeaux, France.</affiliation></author><author><persName><forename type="first">Erwan</forename><surname>Bezard</surname></persName><note type="biography">Erwan Bezard is a research director at INSERM, France. He is best known for his work on the compensatory mechanisms that mask the progression of Parkinson's disease and on the pathophysiology of levodopa-induced dyskinesia. His current research interests include the study of the levodopa-induced dyskinesia and the development of new strategies to alleviate symptoms and/or slow disease progression.</note><affiliation>Erwan Bezard is a research director at INSERM, France. He is best known for his work on the compensatory mechanisms that mask the progression of Parkinson's disease and on the pathophysiology of levodopa-induced dyskinesia. His current research interests include the study of the levodopa-induced dyskinesia and the development of new strategies to alleviate symptoms and/or slow disease progression.</affiliation><affiliation>Service de Neurologie et Centre de référence atrophie multisystématisée, CHU de Bordeaux, Avenue Magellan F-33604 Pessac France.</affiliation><affiliation>CNRS, Institut des Maladies Neurodégénératives, UMR 5293, F-33000 Bordeaux, France.</affiliation></author></analytic><monogr><title level="j">Nature Reviews Drug Discovery</title><idno type="pISSN">1474-1776</idno><idno type="eISSN">1474-1784</idno><imprint><publisher>Nature Publishing Group, a division of Macmillan Publishers Limited. All Rights Reserved.</publisher><date type="published" when="2011-05"></date><biblScope unit="volume">10</biblScope><biblScope unit="issue">5</biblScope><biblScope unit="page" from="377">377</biblScope><biblScope unit="page" to="393">393</biblScope></imprint></monogr><idno type="istex">B18DB94A38D88A12D621F99E69D4EEFEBBE7059E</idno><idno type="DOI">10.1038/nrd3430</idno><idno type="ArticleID">nrd3430</idno></biblStruct></sourceDesc></fileDesc><profileDesc><creation><date>2011-04-29</date></creation><langUsage><language ident="en">en</language></langUsage><abstract xml:lang="en"><p>The loss of dopaminergic neurons in the substantia nigra pars compacta leads to the characteristic motor symptoms of Parkinson's disease: bradykinesia, rigidity and resting tremors. Although these symptoms can be improved using currently available dopamine replacement strategies, there is still a need to improve current strategies of treating these symptoms, together with a need to alleviate non-motor symptoms of the disease. Moreover, treatments that provide neuroprotection and/or disease-modifying effects remain an urgent unmet clinical need. This Review describes the most promising biological targets and therapeutic agents that are currently being assessed to address these treatment goals. Progress will rely on understanding genetic mutations or susceptibility factors that lead to Parkinson's disease, better translation between preclinical animal models and clinical research, and improving the design of future clinical trials.></p></abstract></profileDesc><revisionDesc><change when="2011-04-29">Created</change><change when="2011-05">Published</change></revisionDesc></teiHeader></istex:fulltextTEI><json:item><original>false</original><mimetype>text/plain</mimetype><extension>txt</extension><uri>https://api.istex.fr/document/B18DB94A38D88A12D621F99E69D4EEFEBBE7059E/fulltext/txt</uri></json:item></fulltext><metadata><istex:metadataXml wicri:clean="corpus nature" wicri:toSee="no header"><istex:xmlDeclaration>version="1.0" encoding="UTF-8"</istex:xmlDeclaration><istex:docType PUBLIC="-//NPG//DTD XML Article//EN" URI="NPG_XML_Article.dtd" name="istex:docType"></istex:docType><istex:document><article id="nrd3430" language="eng" origsrc="yes" publish="issue" relation="no"><entity-declarations><entity id="figf1" url="/nrd/journal/v10/n5/images/nrd3430-f1.jpg"></entity><entity id="figf2" url="/nrd/journal/v10/n5/images/nrd3430-f2.jpg"></entity><entity id="tbl1" url="/nrd/journal/v10/n5/images/nrd3430-t1.jpg"></entity><entity id="tbl2" url="/nrd/journal/v10/n5/images/nrd3430-t2.jpg"></entity></entity-declarations><!--nrd3430--><pubfm><jtl>Nature Reviews Drug Discovery</jtl><vol>10</vol><iss>5</iss><idt>201105</idt><categ id="rv"></categ><pp><spn>377</spn><epn>393</epn><cnt>17</cnt></pp><issn type="print">1474-1776</issn><issn type="electronic">1474-1784</issn><cpg><cpy>2011</cpy><cpn>Nature Publishing Group, a division of Macmillan Publishers Limited. All Rights Reserved.</cpn></cpg><subject code="373" id="373" path="/373" priority="0" type="npg.subjects" version="1.0"></subject><subject code="109" id="109" path="/109" priority="0" type="npg.subjects" version="1.0"></subject><subject code="575" id="575" path="/575" priority="0" type="npg.subjects" version="1.0"></subject><doi>10.1038/nrd3430</doi></pubfm><fm><atl display="show">Priorities in Parkinson's disease research</atl><aug><cau><fnm>Wassilios G.</fnm><snm>Meissner</snm><inits>W G</inits><orf rid="a1"></orf><orf rid="a2"></orf><orf rid="a3"></orf><corf rid="c1"></corf><bio><p>Wassilios G. Meissner is Associate Professor of Neurology at the University of Bordeaux, France. He is a clinical neurologist and basic neuroscientist with a specialization in Parkinson's disease (PD) and related disorders. His current research interests focus on multiple system atrophy, (biological and clinical markers of disease progression, development of disease-modifying or neuroprotective strategies), and the development of innovative techniques for deep brain stimulation in PD.</p></bio></cau><au><fnm>Mark</fnm><snm>Frasier</snm><inits>M</inits><orf rid="a4"></orf><bio><p>Mark Frasier, Ph.D, is the Director of Research Programs for the Michael J. Fox Foundation (MJFF), New York, USA. His research interests have focused on drug development in neuroscience and protein folding in neurodegeneration. His current responsibilities include managing the translational research portfolio at MJFF with a focus on biomarkers of Parkinson's disease.</p></bio></au><au><fnm>Thomas</fnm><snm>Gasser</snm><inits>T</inits><orf rid="a5"></orf><bio><p>Thomas Gasser studied medicine at the University of Freiburg, Germany, and Yale University, New Haven, Connecticut, USA. He is Professor of Neurology and Director of the Department for Neurodegenerative Diseases at the Hertie Institute for Clinical Brain Research, Germany, and speaker of the German Center for Neurodegenerative Diseases in Tübingen (DZNE Tübingen), Germany. His research interests include genetics and the molecular basis of Parkinson's disease and other movement disorders.</p></bio></au><au><fnm>Christopher G.</fnm><snm>Goetz</snm><inits>C G</inits><orf rid="a6"></orf><bio><p>Christopher G. Goetz is a clinical neurologist with a primary interest in Parkinson's disease and its complications, specifically dyskinesias and hallucinations. He is actively involved in the development of rating scales and testing of new scales. His research is funded by the US National Institutes of Health, the Michael J. Fox Foundation, and the Parkinson's Disease Foundation.</p></bio></au><au><fnm>Andres</fnm><snm>Lozano</snm><inits>A</inits><orf rid="a7"></orf><bio><p>Andres Lozano is Professor and Chairman of Neurosurgery at the University of Toronto, Canada, and holds both the RR Tasker Chair in Functional Neurosurgery and a Tier 1 Canada Research Chair in Neuroscience. His laboratory is dedicated to the study of neuronal degeneration and regeneration and functional neurosurgery.</p></bio></au><au><fnm>Paola</fnm><snm>Piccini</snm><inits>P</inits><orf rid="a8"></orf><bio><p>Paola Piccini is Professor of Clinical Neurology at Imperial College London (Division of Experimental Medicine), a consultant in neurology with the Imperial College Healthcare NHS Trust and Honorary Professor at the University of Lund, Sweden. She has worked extensively in the field of movement disorders and predominantly on the use of positron emission tomography as a method of investigating the aetiology, effects and complications of therapies, particularly new neuroprotective and neurorestorative therapies in Parkinson's disease and Huntington's disease.</p></bio></au><au><fnm>José A.</fnm><snm>Obeso</snm><inits>J A</inits><orf rid="a9"></orf><bio><p>José A. Obeso graduated from the University of Navarra, Pamplona, Spain, in 1976 and trained in neurology and neurophysiology in San Sebastian and Pamplona, Spain. He is currently Professor of Neurology and a consultant in the Medical School and University Hospital, University of Navarra, and senior researcher at the Centre for Applied Medical Research (CIMA), at the University of Navarra. His research activity focuses on the mechanisms underlying the onset of Parkinson's disease.</p></bio></au><au><fnm>Olivier</fnm><snm>Rascol</snm><inits>O</inits><orf rid="a10"></orf><bio><p>Olivier Rascol M.D., Ph.D. is a neuroscientist and Professor of Clinical Pharmacology at Toulouse University Hospital, France. His main research field is Parkinson's disease (PD), clinical neuropharmacology and functional imaging, and he is actively contributing to the development of novel dopaminergic and non-dopaminergic medications for PD, including disease-modifying agents and symptomatic therapies for motor and non-motor symptoms.</p></bio></au><au><fnm>Anthony</fnm><snm>Schapira</snm><inits>A</inits><orf rid="a11"></orf><bio><p>Anthony Schapira, M.D., D.Sc, FRCP FMedSci, was appointed in 1990 as Chairman of the University Department of Clinical Neurosciences at the Institute of Neurology, UK, and Professor of Neurology at the National Hospital for Neurology and Neurosurgery, UK, and the Royal Free Hospital, UK. He is currently the Vice Dean of University College London Medical School, UK, and Director of the Royal Free Campus of the Medical School.</p></bio></au><au><fnm>Valerie</fnm><snm>Voon</snm><inits>V</inits><orf rid="a12"></orf><bio><p>Valerie Voon, M.D. Ph.D., is a neuropsychiatrist at the University of Cambridge, UK, and a Wellcome Trust Clinical Fellow. Her research focuses on mechanisms underlying impulsive and compulsive disorders in the general population and neurological disorders and utilizes cognitive paradigms, functional MRI and drug manipulation in clinical populations.</p></bio></au><au><fnm>David M.</fnm><snm>Weiner</snm><inits>D M</inits><orf rid="a13"></orf><bio><p>David Weiner is a neurologist and neuropharmacologist who works on translational research in central nervous system diseases, including preclinical development efforts on compounds for schizophrenia, Parkinson's disease and sleep at Acadia Pharmaceuticals, California, USA; most recently, he led the early clinical development efforts in neurodegenerative diseases at EMD/Merck Serono.</p></bio></au><au><fnm>François</fnm><snm>Tison</snm><inits>F</inits><orf rid="a1"></orf><orf rid="a2"></orf><orf rid="a3"></orf><bio><p>François Tison is Professor of Neurology at the University of Bordeaux and deputy director of the Institute of Neurodegenerative Diseases (clinical branch) in Bordeaux, France. He is head of the Parkinsonism and Movement Disorders unit and reference centre for multiple system atrophy at the University Hospital of Bordeaux, France. His main research interests in Parkinson's disease are levodopa-induced dyskinesias, epidemiology, genetics, neuropharmacology, sleep and dementia.</p></bio></au><au><fnm>Erwan</fnm><snm>Bezard</snm><inits>E</inits><orf rid="a1"></orf><orf rid="a3"></orf><bio><p>Erwan Bezard is a research director at INSERM, France. He is best known for his work on the compensatory mechanisms that mask the progression of Parkinson's disease and on the pathophysiology of levodopa-induced dyskinesia. His current research interests include the study of the levodopa-induced dyskinesia and the development of new strategies to alleviate symptoms and/or slow disease progression.</p></bio></au><aff><oid id="a1"></oid><org>Service de Neurologie et Centre de référence atrophie multisystématisée, CHU de Bordeaux</org>, <street>Avenue Magellan</street><zip>F-33604</zip><st>Pessac</st><cny>France</cny>.</aff><aff><oid id="a2"></oid><org>Université de Bordeaux, Institut des Maladies Neurodégénératives</org>, <street>UMR 5293</street>, <zip>F-33000</zip><st>Bordeaux</st>, <cny>France</cny>.</aff><aff><oid id="a3"></oid><org>CNRS, Institut des Maladies Neurodégénératives</org>, <street>UMR 5293</street>, <zip>F-33000</zip><st>Bordeaux</st>, <cny>France</cny>.</aff><aff><oid id="a4"></oid><org>Michael J. Fox Foundation for Parkinson's Research</org>, <cty>New York</cty>, <st>New York</st><zip>10004</zip>, <cny>USA</cny>.</aff><aff><oid id="a5"></oid><org>Department of Neurodegenerative Diseases, Hertie Institute for Clinical Brain Research, University of Tübingen and DZNE — German Center for Neurodegenerative Diseases</org>, <zip>D-72076</zip><st>Tübingen</st>, <cny>Germany</cny>.</aff><aff><oid id="a6"></oid><org>Department of Neurological Sciences, Rush University Medical Center</org>, <cty>Chicago</cty>, <st>Illinois</st><zip>60612</zip>, <cny>USA</cny>.</aff><aff><oid id="a7"></oid><org>Department of Neurosurgery, Toronto Western Hospital, University of Toronto</org>, <cty>Toronto</cty>, <st>Ontario</st><zip>M5T 2S8</zip>, <cny>Canada</cny>.</aff><aff><oid id="a8"></oid><org>Centre for Neuroscience, Imperial College London</org>, <cty>London</cty>, <zip>SW7 2AZ</zip>, <cny>UK</cny>.</aff><aff><oid id="a9"></oid><org>Movement Disorders Group, Neurosciences Division, CIMA, and Department of Neurology and Neurosurgery, Clínica Universitaria and CIBERNED, University of Navarra</org>, <zip>31008</zip><st>Pamplona</st>, <cny>Spain</cny>.</aff><aff><oid id="a10"></oid><org>Departments of Clinical Pharmacology and Neurosciences, INSERM CIC9302, University Hospital of Toulouse</org>, <zip>31000</zip><st>Toulouse</st>, <cny>France</cny>.</aff><aff><oid id="a11"></oid><org>Department of Clinical Neurosciences, Institute of Neurology, University College London</org>, <st>London</st><zip>NW3 2PF</zip>, <cny>UK</cny>.</aff><aff><oid id="a12"></oid><org>Behavioral and Clinical Neurosciences Institute, University of Cambridge</org>, <st>Cambridge</st><zip>CB2 0SZ</zip>, <cny>UK</cny>.</aff><aff><oid id="a13"></oid><org>EMD Serono</org>, <cty>Rockland</cty>, <st>Massachusetts</st><zip>02370</zip>, <cny>USA</cny>.</aff><caff><coid id="c1"></coid><email>wassilios.meissner@chu-bordeaux.fr</email></caff></aug><hst><pubdate day="29" month="04" type="iss" year="2011"></pubdate></hst><execsumm><p><list id="l1" type="bullet"><li>Despite recent advances in the treatment of Parkinson's disease (PD), dyskinesia and motor fluctuations still make a substantial contribution to the reduced quality of life of patients with advanced-stage PD. Additionally, non-motor signs such as depression, dementia, sleep abnormalities and autonomic failure are increasingly being recognized as challenges to effective treatment as they dominate the clinical, caregiver and financial burden of the later stages of PD.</li><li>The translational value of current preclinical models of neurodegeneration remains unsatisfactory. Current limitations could be overcome in a number of ways; for example, by obtaining combinations of mutations by breeding mice with single or dual mutations, or by challenging existing models with environmental stressors such as neurotoxins or neuroinflammation inducers in animals with an established and stable background.</li><li>Novel drug targets will be uncovered through pathophysiological insights gained from the identification of the role of genetic mutations that are responsible for hereditary forms of PD, and future therapies targeted towards these mutations will have broader efficacy against sporadic PD than the currently available symptomatic treatments.</li><li>Many of the therapies that are currently under development — both dopaminergic and non-dopaminergic compounds — are focused on improving motor control, fluctuations and dyskinesias. Far fewer approaches address the other two key unmet clinical needs: specifically, alleviating non-motor symptoms, and disease modification and/or neuroprotection.</li><li>The most promising strategy to achieve disease modification or neuroprotection seems to be a combination of compounds that interfere simultaneously with different key events of PD pathology. This approach would require collaboration between the pharmaceutical companies that hold the patent rights of the different compounds.</li><li>Primary end points in past and ongoing trials of potential disease-modifying or neuroprotective drugs rely on clinical assessment scales. Additional efforts are therefore urgently needed to establish validated biomarkers in PD.</li></list></p></execsumm><websumm>Neuroprotective and/or disease-modifying treatments are urgently needed for Parkinson's disease. This Review describes how an increased understanding of genetic mutations that lead to Parkinson's disease, better translation between preclinical animal models and clinical research, and improved design of future clinical trials are priorities for overcoming the limitations of current therapies.</websumm><abs><p>The loss of dopaminergic neurons in the substantia nigra pars compacta leads to the characteristic motor symptoms of Parkinson's disease: bradykinesia, rigidity and resting tremors. Although these symptoms can be improved using currently available dopamine replacement strategies, there is still a need to improve current strategies of treating these symptoms, together with a need to alleviate non-motor symptoms of the disease. Moreover, treatments that provide neuroprotection and/or disease-modifying effects remain an urgent unmet clinical need. This Review describes the most promising biological targets and therapeutic agents that are currently being assessed to address these treatment goals. Progress will rely on understanding genetic mutations or susceptibility factors that lead to Parkinson's disease, better translation between preclinical animal models and clinical research, and improving the design of future clinical trials.></p></abs></fm></article></istex:document></istex:metadataXml><mods version="3.6"><titleInfo lang="eng"><title>Priorities in Parkinson's disease research</title></titleInfo><titleInfo type="alternative" lang="eng" contentType="CDATA"><title>Priorities in Parkinson's disease research</title></titleInfo><name type="personal"><namePart type="given">Wassilios G.</namePart><namePart type="family">Meissner</namePart><affiliation>Service de Neurologie et Centre de référence atrophie multisystématisée, CHU de Bordeaux, Avenue Magellan F-33604 Pessac France.</affiliation><affiliation>Université de Bordeaux, Institut des Maladies Neurodégénératives, UMR 5293, F-33000 Bordeaux, France.</affiliation><affiliation>CNRS, Institut des Maladies Neurodégénératives, UMR 5293, F-33000 Bordeaux, France.</affiliation><affiliation>E-mail: wassilios.meissner@chu-bordeaux.fr</affiliation><role><roleTerm type="text">author</roleTerm></role><description>Wassilios G. Meissner is Associate Professor of Neurology at the University of Bordeaux, France. He is a clinical neurologist and basic neuroscientist with a specialization in Parkinson's disease (PD) and related disorders. His current research interests focus on multiple system atrophy, (biological and clinical markers of disease progression, development of disease-modifying or neuroprotective strategies), and the development of innovative techniques for deep brain stimulation in PD.</description></name><name type="personal"><namePart type="given">Mark</namePart><namePart type="family">Frasier</namePart><affiliation>Michael J. Fox Foundation for Parkinson's Research, New York, New York 10004, USA.</affiliation><role><roleTerm type="text">author</roleTerm></role><description>Mark Frasier, Ph.D, is the Director of Research Programs for the Michael J. Fox Foundation (MJFF), New York, USA. His research interests have focused on drug development in neuroscience and protein folding in neurodegeneration. His current responsibilities include managing the translational research portfolio at MJFF with a focus on biomarkers of Parkinson's disease.</description></name><name type="personal"><namePart type="given">Thomas</namePart><namePart type="family">Gasser</namePart><affiliation>Department of Neurodegenerative Diseases, Hertie Institute for Clinical Brain Research, University of Tübingen and DZNE — German Center for Neurodegenerative Diseases, D-72076 Tübingen, Germany.</affiliation><role><roleTerm type="text">author</roleTerm></role><description>Thomas Gasser studied medicine at the University of Freiburg, Germany, and Yale University, New Haven, Connecticut, USA. He is Professor of Neurology and Director of the Department for Neurodegenerative Diseases at the Hertie Institute for Clinical Brain Research, Germany, and speaker of the German Center for Neurodegenerative Diseases in Tübingen (DZNE Tübingen), Germany. His research interests include genetics and the molecular basis of Parkinson's disease and other movement disorders.</description></name><name type="personal"><namePart type="given">Christopher G.</namePart><namePart type="family">Goetz</namePart><affiliation>Department of Neurological Sciences, Rush University Medical Center, Chicago, Illinois 60612, USA.</affiliation><role><roleTerm type="text">author</roleTerm></role><description>Christopher G. Goetz is a clinical neurologist with a primary interest in Parkinson's disease and its complications, specifically dyskinesias and hallucinations. He is actively involved in the development of rating scales and testing of new scales. His research is funded by the US National Institutes of Health, the Michael J. Fox Foundation, and the Parkinson's Disease Foundation.</description></name><name type="personal"><namePart type="given">Andres</namePart><namePart type="family">Lozano</namePart><affiliation>Department of Neurosurgery, Toronto Western Hospital, University of Toronto, Toronto, Ontario M5T 2S8, Canada.</affiliation><role><roleTerm type="text">author</roleTerm></role><description>Andres Lozano is Professor and Chairman of Neurosurgery at the University of Toronto, Canada, and holds both the RR Tasker Chair in Functional Neurosurgery and a Tier 1 Canada Research Chair in Neuroscience. His laboratory is dedicated to the study of neuronal degeneration and regeneration and functional neurosurgery.</description></name><name type="personal"><namePart type="given">Paola</namePart><namePart type="family">Piccini</namePart><affiliation>Centre for Neuroscience, Imperial College London, London, SW7 2AZ, UK.</affiliation><role><roleTerm type="text">author</roleTerm></role><description>Paola Piccini is Professor of Clinical Neurology at Imperial College London (Division of Experimental Medicine), a consultant in neurology with the Imperial College Healthcare NHS Trust and Honorary Professor at the University of Lund, Sweden. She has worked extensively in the field of movement disorders and predominantly on the use of positron emission tomography as a method of investigating the aetiology, effects and complications of therapies, particularly new neuroprotective and neurorestorative therapies in Parkinson's disease and Huntington's disease.</description></name><name type="personal"><namePart type="given">José A.</namePart><namePart type="family">Obeso</namePart><affiliation>Movement Disorders Group, Neurosciences Division, CIMA, and Department of Neurology and Neurosurgery, Clínica Universitaria and CIBERNED, University of Navarra, 31008 Pamplona, Spain.</affiliation><role><roleTerm type="text">author</roleTerm></role><description>José A. Obeso graduated from the University of Navarra, Pamplona, Spain, in 1976 and trained in neurology and neurophysiology in San Sebastian and Pamplona, Spain. He is currently Professor of Neurology and a consultant in the Medical School and University Hospital, University of Navarra, and senior researcher at the Centre for Applied Medical Research (CIMA), at the University of Navarra. His research activity focuses on the mechanisms underlying the onset of Parkinson's disease.</description></name><name type="personal"><namePart type="given">Olivier</namePart><namePart type="family">Rascol</namePart><affiliation>Departments of Clinical Pharmacology and Neurosciences, INSERM CIC9302, University Hospital of Toulouse, 31000 Toulouse, France.</affiliation><role><roleTerm type="text">author</roleTerm></role><description>Olivier Rascol M.D., Ph.D. is a neuroscientist and Professor of Clinical Pharmacology at Toulouse University Hospital, France. His main research field is Parkinson's disease (PD), clinical neuropharmacology and functional imaging, and he is actively contributing to the development of novel dopaminergic and non-dopaminergic medications for PD, including disease-modifying agents and symptomatic therapies for motor and non-motor symptoms.</description></name><name type="personal"><namePart type="given">Anthony</namePart><namePart type="family">Schapira</namePart><affiliation>Department of Clinical Neurosciences, Institute of Neurology, University College London, London NW3 2PF, UK.</affiliation><role><roleTerm type="text">author</roleTerm></role><description>Anthony Schapira, M.D., D.Sc, FRCP FMedSci, was appointed in 1990 as Chairman of the University Department of Clinical Neurosciences at the Institute of Neurology, UK, and Professor of Neurology at the National Hospital for Neurology and Neurosurgery, UK, and the Royal Free Hospital, UK. He is currently the Vice Dean of University College London Medical School, UK, and Director of the Royal Free Campus of the Medical School.</description></name><name type="personal"><namePart type="given">Valerie</namePart><namePart type="family">Voon</namePart><affiliation>Behavioral and Clinical Neurosciences Institute, University of Cambridge, Cambridge CB2 0SZ, UK.</affiliation><role><roleTerm type="text">author</roleTerm></role><description>Valerie Voon, M.D. Ph.D., is a neuropsychiatrist at the University of Cambridge, UK, and a Wellcome Trust Clinical Fellow. Her research focuses on mechanisms underlying impulsive and compulsive disorders in the general population and neurological disorders and utilizes cognitive paradigms, functional MRI and drug manipulation in clinical populations.</description></name><name type="personal"><namePart type="given">David M.</namePart><namePart type="family">Weiner</namePart><affiliation>EMD Serono, Rockland, Massachusetts 02370, USA.</affiliation><role><roleTerm type="text">author</roleTerm></role><description>David Weiner is a neurologist and neuropharmacologist who works on translational research in central nervous system diseases, including preclinical development efforts on compounds for schizophrenia, Parkinson's disease and sleep at Acadia Pharmaceuticals, California, USA; most recently, he led the early clinical development efforts in neurodegenerative diseases at EMD/Merck Serono.</description></name><name type="personal"><namePart type="given">François</namePart><namePart type="family">Tison</namePart><affiliation>Service de Neurologie et Centre de référence atrophie multisystématisée, CHU de Bordeaux, Avenue Magellan F-33604 Pessac France.</affiliation><affiliation>Université de Bordeaux, Institut des Maladies Neurodégénératives, UMR 5293, F-33000 Bordeaux, France.</affiliation><affiliation>CNRS, Institut des Maladies Neurodégénératives, UMR 5293, F-33000 Bordeaux, France.</affiliation><role><roleTerm type="text">author</roleTerm></role><description>François Tison is Professor of Neurology at the University of Bordeaux and deputy director of the Institute of Neurodegenerative Diseases (clinical branch) in Bordeaux, France. He is head of the Parkinsonism and Movement Disorders unit and reference centre for multiple system atrophy at the University Hospital of Bordeaux, France. His main research interests in Parkinson's disease are levodopa-induced dyskinesias, epidemiology, genetics, neuropharmacology, sleep and dementia.</description></name><name type="personal"><namePart type="given">Erwan</namePart><namePart type="family">Bezard</namePart><affiliation>Service de Neurologie et Centre de référence atrophie multisystématisée, CHU de Bordeaux, Avenue Magellan F-33604 Pessac France.</affiliation><affiliation>CNRS, Institut des Maladies Neurodégénératives, UMR 5293, F-33000 Bordeaux, France.</affiliation><role><roleTerm type="text">author</roleTerm></role><description>Erwan Bezard is a research director at INSERM, France. He is best known for his work on the compensatory mechanisms that mask the progression of Parkinson's disease and on the pathophysiology of levodopa-induced dyskinesia. His current research interests include the study of the levodopa-induced dyskinesia and the development of new strategies to alleviate symptoms and/or slow disease progression.</description></name><typeOfResource>text</typeOfResource><genre type="review-article" displayLabel="Review"></genre><originInfo><publisher>Nature Publishing Group, a division of Macmillan Publishers Limited. All Rights Reserved.</publisher><dateIssued encoding="w3cdtf">2011-05</dateIssued><dateCreated encoding="w3cdtf">2011-04-29</dateCreated><copyrightDate encoding="w3cdtf">2011</copyrightDate></originInfo><language><languageTerm type="code" authority="iso639-2b">eng</languageTerm><languageTerm type="code" authority="rfc3066">en</languageTerm></language><physicalDescription><internetMediaType>text/html</internetMediaType></physicalDescription><abstract lang="eng">The loss of dopaminergic neurons in the substantia nigra pars compacta leads to the characteristic motor symptoms of Parkinson's disease: bradykinesia, rigidity and resting tremors. Although these symptoms can be improved using currently available dopamine replacement strategies, there is still a need to improve current strategies of treating these symptoms, together with a need to alleviate non-motor symptoms of the disease. Moreover, treatments that provide neuroprotection and/or disease-modifying effects remain an urgent unmet clinical need. This Review describes the most promising biological targets and therapeutic agents that are currently being assessed to address these treatment goals. Progress will rely on understanding genetic mutations or susceptibility factors that lead to Parkinson's disease, better translation between preclinical animal models and clinical research, and improving the design of future clinical trials.></abstract><relatedItem type="host"><titleInfo><title>Nature Reviews Drug Discovery</title></titleInfo><classification displayLabel="373"></classification><classification displayLabel="109"></classification><classification displayLabel="575"></classification><identifier type="ISSN">1474-1776</identifier><identifier type="eISSN">1474-1784</identifier><part><date>2011</date><detail type="volume"><caption>vol.</caption><number>10</number></detail><detail type="issue"><caption>no.</caption><number>5</number></detail><extent unit="pages"><start>377</start><end>393</end><total>17</total></extent></part></relatedItem><identifier type="istex">B18DB94A38D88A12D621F99E69D4EEFEBBE7059E</identifier><identifier type="DOI">10.1038/nrd3430</identifier><identifier type="ArticleID">nrd3430</identifier><accessCondition type="use and reproduction" contentType="copyright">©2011 Nature Publishing Group, a division of Macmillan Publishers Limited. 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