Why have we failed to achieve neuroprotection in Parkinson's disease?
Identifieur interne : 000118 ( Main/Corpus ); précédent : 000117; suivant : 000119Why have we failed to achieve neuroprotection in Parkinson's disease?
Auteurs : C. Warren Olanow ; Karl Kieburtz ; Anthony H. V. SchapiraSource :
- Annals of Neurology [ 0364-5134 ] ; 2008-12.
Abstract
The development of a neuroprotective therapy that slows, stops, or reverses neurodegeneration in Parkinson's disease (PD) is the single most important unresolved issue in the management of this disorder. Current therapies provide effective control of symptoms, particularly in the early stages of the disease, but disease progression is associated with the development of “nondopaminergic” features such as postural instability, falling, and dementia that are not adequately controlled with existing medications. There are many promising candidate neuroprotective agents based on pathological and laboratory studies, but to date, it has not been possible to determine that any drug has a disease‐modifying effect in PD. Obstacles to the development of a neuroprotective therapy in PD include: (1) uncertainty as to the precise cause of cell death in PD and what to target; (2) the lack of an animal model of PD that precisely reflects the etiopathogenesis of the disease, the pattern of dopaminergic and nondopaminergic pathology, and its chronic, progressive nature; (3) determination of the correct dose to use in clinical trials; and (4) delineation of a clinical end point that is an accurate measure of the underlying disease and is not confounded by potential symptomatic effects of a study intervention. New developments in understanding the cause of the disease, in the development of animal models of PD, and in clinical trial methodology will hopefully hasten the resolution of these problems. Ann Neurol 2008;64 (suppl):S101–S110
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DOI: 10.1002/ana.21461
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Warren Olanow</name><affiliation><mods:affiliation>Departments of Neurology and Neuroscience, Mount Sinai School of Medicine, New York</mods:affiliation></affiliation></author><author><name sortKey="Kieburtz, Karl" sort="Kieburtz, Karl" uniqKey="Kieburtz K" first="Karl" last="Kieburtz">Karl Kieburtz</name><affiliation><mods:affiliation>Department of Neurology, University of Rochester, Rochester, NY</mods:affiliation></affiliation></author><author><name sortKey="Schapira, Anthony H V" sort="Schapira, Anthony H V" uniqKey="Schapira A" first="Anthony H. V." last="Schapira">Anthony H. V. 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Current therapies provide effective control of symptoms, particularly in the early stages of the disease, but disease progression is associated with the development of “nondopaminergic” features such as postural instability, falling, and dementia that are not adequately controlled with existing medications. There are many promising candidate neuroprotective agents based on pathological and laboratory studies, but to date, it has not been possible to determine that any drug has a disease‐modifying effect in PD. Obstacles to the development of a neuroprotective therapy in PD include: (1) uncertainty as to the precise cause of cell death in PD and what to target; (2) the lack of an animal model of PD that precisely reflects the etiopathogenesis of the disease, the pattern of dopaminergic and nondopaminergic pathology, and its chronic, progressive nature; (3) determination of the correct dose to use in clinical trials; and (4) delineation of a clinical end point that is an accurate measure of the underlying disease and is not confounded by potential symptomatic effects of a study intervention. New developments in understanding the cause of the disease, in the development of animal models of PD, and in clinical trial methodology will hopefully hasten the resolution of these problems. Ann Neurol 2008;64 (suppl):S101–S110</div></front></TEI><istex><corpusName>wiley</corpusName><author><json:item><name>C. Warren Olanow MD, FRCPC</name><affiliations><json:string>Departments of Neurology and Neuroscience, Mount Sinai School of Medicine, New York</json:string></affiliations></json:item><json:item><name>Karl Kieburtz MD</name><affiliations><json:string>Department of Neurology, University of Rochester, Rochester, NY</json:string></affiliations></json:item><json:item><name>Anthony H. V. Schapira MD</name><affiliations><json:string>University Department of Clinical Neurosciences, Royal Free and University College Medical School, and Institute of Neurology, Queen Square, London, United Kingdom</json:string></affiliations></json:item></author><articleId><json:string>ANA21461</json:string></articleId><language><json:string>eng</json:string></language><abstract>The development of a neuroprotective therapy that slows, stops, or reverses neurodegeneration in Parkinson's disease (PD) is the single most important unresolved issue in the management of this disorder. Current therapies provide effective control of symptoms, particularly in the early stages of the disease, but disease progression is associated with the development of “nondopaminergic” features such as postural instability, falling, and dementia that are not adequately controlled with existing medications. There are many promising candidate neuroprotective agents based on pathological and laboratory studies, but to date, it has not been possible to determine that any drug has a disease‐modifying effect in PD. Obstacles to the development of a neuroprotective therapy in PD include: (1) uncertainty as to the precise cause of cell death in PD and what to target; (2) the lack of an animal model of PD that precisely reflects the etiopathogenesis of the disease, the pattern of dopaminergic and nondopaminergic pathology, and its chronic, progressive nature; (3) determination of the correct dose to use in clinical trials; and (4) delineation of a clinical end point that is an accurate measure of the underlying disease and is not confounded by potential symptomatic effects of a study intervention. New developments in understanding the cause of the disease, in the development of animal models of PD, and in clinical trial methodology will hopefully hasten the resolution of these problems. 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C.W.O. has served as a consultant to BI, Novartis, Teva, Merck Serono, and Ceregene. K.K. currently serves as principal investigator for a clinical trial of pramipexole, sponsored by BI. K.K. also receives grant support from Amarin, Medivation, and Neurosearch. K.K. has served as a consultant for Abbott, Antipodean, Biogen Idec, Ceregene, Eisai, FoldRx, Impax, Ipsen, Lilly, Lundbeck, Merck‐Serono, Merz, Novartis, Orion, Pfizer, Prestwick, Schering‐Plough, Schwarz, Solvay, Teva, UCB Pharma, and Vernalis. A.H.V.S. has received honoraria as a consultant for BI, GlaxoSmithKline, Treva, Lundbeck, Novartis, Orion, and Solvay.</note></notesStmt><sourceDesc><biblStruct type="inbook"><analytic><title level="a" type="main" xml:lang="en">Why have we failed to achieve neuroprotection in Parkinson's disease?</title><author><persName><forename type="first">C. Warren</forename><surname>Olanow</surname></persName><roleName type="degree">MD, FRCPC</roleName><note type="correspondence"><p>Correspondence: Department of Neurology, Mount Sinai Medical Center, 1 Gustave Levy Place, Annenberg 14‐94, New York, NY 10029</p></note><affiliation>Departments of Neurology and Neuroscience, Mount Sinai School of Medicine, New York</affiliation></author><author><persName><forename type="first">Karl</forename><surname>Kieburtz</surname></persName><roleName type="degree">MD</roleName><affiliation>Department of Neurology, University of Rochester, Rochester, NY</affiliation></author><author><persName><forename type="first">Anthony H. 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Current therapies provide effective control of symptoms, particularly in the early stages of the disease, but disease progression is associated with the development of “nondopaminergic” features such as postural instability, falling, and dementia that are not adequately controlled with existing medications. There are many promising candidate neuroprotective agents based on pathological and laboratory studies, but to date, it has not been possible to determine that any drug has a disease‐modifying effect in PD. Obstacles to the development of a neuroprotective therapy in PD include: (1) uncertainty as to the precise cause of cell death in PD and what to target; (2) the lack of an animal model of PD that precisely reflects the etiopathogenesis of the disease, the pattern of dopaminergic and nondopaminergic pathology, and its chronic, progressive nature; (3) determination of the correct dose to use in clinical trials; and (4) delineation of a clinical end point that is an accurate measure of the underlying disease and is not confounded by potential symptomatic effects of a study intervention. New developments in understanding the cause of the disease, in the development of animal models of PD, and in clinical trial methodology will hopefully hasten the resolution of these problems. 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Warren</givenNames><familyName>Olanow</familyName><degrees>MD, FRCPC</degrees></personName><contactDetails><email>warren.olanow@mssm.edu</email></contactDetails></creator><creator xml:id="au2" creatorRole="author" affiliationRef="#af2"><personName><givenNames>Karl</givenNames><familyName>Kieburtz</familyName><degrees>MD</degrees></personName></creator><creator xml:id="au3" creatorRole="author" affiliationRef="#af3"><personName><givenNames>Anthony H. V.</givenNames><familyName>Schapira</familyName><degrees>MD</degrees></personName></creator></creators><affiliationGroup><affiliation xml:id="af1" countryCode="US" type="organization"><unparsedAffiliation>Departments of Neurology and Neuroscience, Mount Sinai School of Medicine, New York</unparsedAffiliation></affiliation><affiliation xml:id="af2" countryCode="US" type="organization"><unparsedAffiliation>Department of Neurology, University of Rochester, Rochester, NY</unparsedAffiliation></affiliation><affiliation xml:id="af3" countryCode="GB" type="organization"><unparsedAffiliation>University Department of Clinical Neurosciences, Royal Free and University College Medical School, and Institute of Neurology, Queen Square, London, United Kingdom</unparsedAffiliation></affiliation></affiliationGroup><abstractGroup><abstract type="main" xml:lang="en"><title type="main">Abstract</title><p>The development of a neuroprotective therapy that slows, stops, or reverses neurodegeneration in Parkinson's disease (PD) is the single most important unresolved issue in the management of this disorder. Current therapies provide effective control of symptoms, particularly in the early stages of the disease, but disease progression is associated with the development of “nondopaminergic” features such as postural instability, falling, and dementia that are not adequately controlled with existing medications. There are many promising candidate neuroprotective agents based on pathological and laboratory studies, but to date, it has not been possible to determine that any drug has a disease‐modifying effect in PD. Obstacles to the development of a neuroprotective therapy in PD include: (1) uncertainty as to the precise cause of cell death in PD and what to target; (2) the lack of an animal model of PD that precisely reflects the etiopathogenesis of the disease, the pattern of dopaminergic and nondopaminergic pathology, and its chronic, progressive nature; (3) determination of the correct dose to use in clinical trials; and (4) delineation of a clinical end point that is an accurate measure of the underlying disease and is not confounded by potential symptomatic effects of a study intervention. New developments in understanding the cause of the disease, in the development of animal models of PD, and in clinical trial methodology will hopefully hasten the resolution of these problems. Ann Neurol 2008;64 (suppl):S101–S110</p></abstract></abstractGroup></contentMeta><noteGroup><note xml:id="fn1"><p>Potential conflict of interest: This article is part of a supplement sponsored by Boehringer Ingelheim (BI). C.W.O. has served as a consultant to BI, Novartis, Teva, Merck Serono, and Ceregene. K.K. currently serves as principal investigator for a clinical trial of pramipexole, sponsored by BI. K.K. also receives grant support from Amarin, Medivation, and Neurosearch. K.K. has served as a consultant for Abbott, Antipodean, Biogen Idec, Ceregene, Eisai, FoldRx, Impax, Ipsen, Lilly, Lundbeck, Merck‐Serono, Merz, Novartis, Orion, Pfizer, Prestwick, Schering‐Plough, Schwarz, Solvay, Teva, UCB Pharma, and Vernalis. A.H.V.S. has received honoraria as a consultant for BI, GlaxoSmithKline, Treva, Lundbeck, Novartis, Orion, and Solvay.</p></note></noteGroup></header></component></istex:document></istex:metadataXml><mods version="3.6"><titleInfo lang="en"><title>Why have we failed to achieve neuroprotection in Parkinson's disease?</title></titleInfo><titleInfo type="abbreviated" lang="en"><title>Neuroprotection in PD</title></titleInfo><titleInfo type="alternative" contentType="CDATA" lang="en"><title>Why have we failed to achieve neuroprotection in Parkinson's disease?</title></titleInfo><name type="personal"><namePart type="given">C. Warren</namePart><namePart type="family">Olanow</namePart><namePart type="termsOfAddress">MD, FRCPC</namePart><affiliation>Departments of Neurology and Neuroscience, Mount Sinai School of Medicine, New York</affiliation><description>Correspondence: Department of Neurology, Mount Sinai Medical Center, 1 Gustave Levy Place, Annenberg 14‐94, New York, NY 10029</description><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Karl</namePart><namePart type="family">Kieburtz</namePart><namePart type="termsOfAddress">MD</namePart><affiliation>Department of Neurology, University of Rochester, Rochester, NY</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Anthony H. V.</namePart><namePart type="family">Schapira</namePart><namePart type="termsOfAddress">MD</namePart><affiliation>University Department of Clinical Neurosciences, Royal Free and University College Medical School, and Institute of Neurology, Queen Square, London, United Kingdom</affiliation><role><roleTerm type="text">author</roleTerm></role></name><typeOfResource>text</typeOfResource><genre type="article" displayLabel="article"></genre><originInfo><publisher>Wiley Subscription Services, Inc., A Wiley Company</publisher><place><placeTerm type="text">Hoboken</placeTerm></place><dateIssued encoding="w3cdtf">2008-12</dateIssued><dateCaptured encoding="w3cdtf">2008-03-19</dateCaptured><dateValid encoding="w3cdtf">2008-06-13</dateValid><copyrightDate encoding="w3cdtf">2008</copyrightDate></originInfo><language><languageTerm type="code" authority="rfc3066">en</languageTerm><languageTerm type="code" authority="iso639-2b">eng</languageTerm></language><physicalDescription><internetMediaType>text/html</internetMediaType><extent unit="figures">1</extent><extent unit="tables">2</extent><extent unit="references">55</extent><extent unit="words">7120</extent></physicalDescription><abstract lang="en">The development of a neuroprotective therapy that slows, stops, or reverses neurodegeneration in Parkinson's disease (PD) is the single most important unresolved issue in the management of this disorder. Current therapies provide effective control of symptoms, particularly in the early stages of the disease, but disease progression is associated with the development of “nondopaminergic” features such as postural instability, falling, and dementia that are not adequately controlled with existing medications. There are many promising candidate neuroprotective agents based on pathological and laboratory studies, but to date, it has not been possible to determine that any drug has a disease‐modifying effect in PD. Obstacles to the development of a neuroprotective therapy in PD include: (1) uncertainty as to the precise cause of cell death in PD and what to target; (2) the lack of an animal model of PD that precisely reflects the etiopathogenesis of the disease, the pattern of dopaminergic and nondopaminergic pathology, and its chronic, progressive nature; (3) determination of the correct dose to use in clinical trials; and (4) delineation of a clinical end point that is an accurate measure of the underlying disease and is not confounded by potential symptomatic effects of a study intervention. New developments in understanding the cause of the disease, in the development of animal models of PD, and in clinical trial methodology will hopefully hasten the resolution of these problems. Ann Neurol 2008;64 (suppl):S101–S110</abstract><note type="content">*Potential conflict of interest: This article is part of a supplement sponsored by Boehringer Ingelheim (BI). C.W.O. has served as a consultant to BI, Novartis, Teva, Merck Serono, and Ceregene. K.K. currently serves as principal investigator for a clinical trial of pramipexole, sponsored by BI. K.K. also receives grant support from Amarin, Medivation, and Neurosearch. K.K. has served as a consultant for Abbott, Antipodean, Biogen Idec, Ceregene, Eisai, FoldRx, Impax, Ipsen, Lilly, Lundbeck, Merck‐Serono, Merz, Novartis, Orion, Pfizer, Prestwick, Schering‐Plough, Schwarz, Solvay, Teva, UCB Pharma, and Vernalis. A.H.V.S. has received honoraria as a consultant for BI, GlaxoSmithKline, Treva, Lundbeck, Novartis, Orion, and Solvay.</note><relatedItem type="host"><titleInfo><title>Annals of Neurology</title><subTitle>Official Journal of the American Neurological Association and the Child Neurology Society</subTitle></titleInfo><titleInfo type="abbreviated"><title>Ann Neurol.</title></titleInfo><genre type="Journal">journal</genre><subject><genre>article category</genre><topic>Clinical Issues</topic></subject><identifier type="ISSN">0364-5134</identifier><identifier type="eISSN">1531-8249</identifier><identifier type="DOI">10.1002/(ISSN)1531-8249</identifier><identifier type="PublisherID">ANA</identifier><part><date>2008</date><detail type="volume"><caption>vol.</caption><number>64</number></detail><detail type="issue"><caption>no.</caption><number>S2</number></detail><detail type="supplement"><caption>Suppl. no.</caption><number>2</number></detail><extent unit="pages"><start>S101</start><end>S110</end><total>10</total></extent></part></relatedItem><identifier type="istex">739F8C3A9D500DFBE678CAD7407D6115CBD8F848</identifier><identifier type="DOI">10.1002/ana.21461</identifier><identifier type="ArticleID">ANA21461</identifier><accessCondition type="use and reproduction" contentType="copyright">Copyright © 2008 American Neurological Association</accessCondition><recordInfo><recordContentSource>WILEY</recordContentSource><recordOrigin>Wiley Subscription Services, Inc., A Wiley Company</recordOrigin></recordInfo></mods></metadata><serie></serie></istex></record>Pour manipuler ce document sous Unix (Dilib)
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