Gene Therapy for Parkinson's Disease: An Approach to the Prevention or Palliation of Levodopa-Associated Motor Complications
Identifieur interne : 002019 ( Main/Corpus ); précédent : 002018; suivant : 002020Gene Therapy for Parkinson's Disease: An Approach to the Prevention or Palliation of Levodopa-Associated Motor Complications
Auteurs : M. Maral Mouradian ; Thomas N. ChaseSource :
- Experimental Neurology [ 0014-4886 ] ; 1997.
Abstract
Gene therapy holds considerable potential for the treatment of central nervous system disease. The introduction of functional genes into the brain of patients with Parkinson's disease may, for example, prove useful as a means to replace a defective gene, introduce a potentially neuroprotective or neurorestorative protein, or permit the physiological delivery of a deficient neurotransmitter. Recent observations suggest that the oral administration of currently available dopaminomimetics to relatively advanced parkinsonian patients leads to nonphysiologic intermittent stimulation of striatal neurons that express dopamine receptors. Resultant activation of signal transduction pathways from these dopaminergic receptors on medium-sized GABAergic neurons apparently induces long-term potentiation of adjacent glutamatergic receptors of theN-methyl-d-aspartate subtype. The effects of dopaminergic drugs thus become modified in ways that favor the clinical appearance of response fluctuations and peak-dose dyskinesias. In parkinsonian models as well as in patients with Parkinson's disease, continuous dopaminergic replacement tends to prevent or alleviate these adverse effects. By continuously maintaining appropriate cerebral dopamine concentrations, molecular techniques which stimulate an increase in the intrastriatal activity of tyrosine hydroxylase, the rate-limiting enzyme for dopamine synthesis, might be expected to palliate parkinsonian symptoms with less risk of the disabling consequences of current therapy. Clinical study of these approaches could also serve as initial, relatively simple, proof-of-principle evaluations of the safety and efficacy of genetic approaches to the treatment of basic disease processes in Parkinson's disease and related neurodegenerative disorders.
Url:
DOI: 10.1006/exnr.1996.6388
Links to Exploration step
ISTEX:A157EE11D81693A2773389872E64B081B653E6FDLe document en format XML
<record><TEI wicri:istexFullTextTei="biblStruct"><teiHeader><fileDesc><titleStmt><title xml:lang="en">Gene Therapy for Parkinson's Disease: An Approach to the Prevention or Palliation of Levodopa-Associated Motor Complications</title><author><name sortKey="Mouradian, M Maral" sort="Mouradian, M Maral" uniqKey="Mouradian M" first="M. Maral" last="Mouradian">M. Maral Mouradian</name><affiliation><mods:affiliation>Experimental Therapeutics Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland, 20892</mods:affiliation></affiliation></author><author><name sortKey="Chase, Thomas N" sort="Chase, Thomas N" uniqKey="Chase T" first="Thomas N." last="Chase">Thomas N. Chase</name><affiliation><mods:affiliation>Experimental Therapeutics Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland, 20892</mods:affiliation></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">ISTEX</idno><idno type="RBID">ISTEX:A157EE11D81693A2773389872E64B081B653E6FD</idno><date when="1997" year="1997">1997</date><idno type="doi">10.1006/exnr.1996.6388</idno><idno type="url">https://api.istex.fr/document/A157EE11D81693A2773389872E64B081B653E6FD/fulltext/pdf</idno><idno type="wicri:Area/Main/Corpus">002019</idno></publicationStmt><sourceDesc><biblStruct><analytic><title level="a" type="main" xml:lang="en">Gene Therapy for Parkinson's Disease: An Approach to the Prevention or Palliation of Levodopa-Associated Motor Complications</title><author><name sortKey="Mouradian, M Maral" sort="Mouradian, M Maral" uniqKey="Mouradian M" first="M. Maral" last="Mouradian">M. Maral Mouradian</name><affiliation><mods:affiliation>Experimental Therapeutics Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland, 20892</mods:affiliation></affiliation></author><author><name sortKey="Chase, Thomas N" sort="Chase, Thomas N" uniqKey="Chase T" first="Thomas N." last="Chase">Thomas N. Chase</name><affiliation><mods:affiliation>Experimental Therapeutics Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland, 20892</mods:affiliation></affiliation></author></analytic><monogr></monogr><series><title level="j">Experimental Neurology</title><title level="j" type="abbrev">YEXNR</title><idno type="ISSN">0014-4886</idno><imprint><publisher>ELSEVIER</publisher><date type="published" when="1997">1997</date><biblScope unit="volume">144</biblScope><biblScope unit="issue">1</biblScope><biblScope unit="page" from="51">51</biblScope><biblScope unit="page" to="57">57</biblScope></imprint><idno type="ISSN">0014-4886</idno></series><idno type="istex">A157EE11D81693A2773389872E64B081B653E6FD</idno><idno type="DOI">10.1006/exnr.1996.6388</idno><idno type="PII">S0014-4886(96)96388-8</idno></biblStruct></sourceDesc><seriesStmt><idno type="ISSN">0014-4886</idno></seriesStmt></fileDesc><profileDesc><textClass></textClass><langUsage><language ident="en">en</language></langUsage></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Gene therapy holds considerable potential for the treatment of central nervous system disease. The introduction of functional genes into the brain of patients with Parkinson's disease may, for example, prove useful as a means to replace a defective gene, introduce a potentially neuroprotective or neurorestorative protein, or permit the physiological delivery of a deficient neurotransmitter. Recent observations suggest that the oral administration of currently available dopaminomimetics to relatively advanced parkinsonian patients leads to nonphysiologic intermittent stimulation of striatal neurons that express dopamine receptors. Resultant activation of signal transduction pathways from these dopaminergic receptors on medium-sized GABAergic neurons apparently induces long-term potentiation of adjacent glutamatergic receptors of theN-methyl-d-aspartate subtype. The effects of dopaminergic drugs thus become modified in ways that favor the clinical appearance of response fluctuations and peak-dose dyskinesias. In parkinsonian models as well as in patients with Parkinson's disease, continuous dopaminergic replacement tends to prevent or alleviate these adverse effects. By continuously maintaining appropriate cerebral dopamine concentrations, molecular techniques which stimulate an increase in the intrastriatal activity of tyrosine hydroxylase, the rate-limiting enzyme for dopamine synthesis, might be expected to palliate parkinsonian symptoms with less risk of the disabling consequences of current therapy. Clinical study of these approaches could also serve as initial, relatively simple, proof-of-principle evaluations of the safety and efficacy of genetic approaches to the treatment of basic disease processes in Parkinson's disease and related neurodegenerative disorders.</div></front></TEI><istex><corpusName>elsevier</corpusName><author><json:item><name>M.Maral Mouradian</name><affiliations><json:string>Experimental Therapeutics Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland, 20892</json:string></affiliations></json:item><json:item><name>Thomas N. Chase</name><affiliations><json:string>Experimental Therapeutics Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland, 20892</json:string></affiliations></json:item></author><language><json:string>eng</json:string></language><abstract>Gene therapy holds considerable potential for the treatment of central nervous system disease. The introduction of functional genes into the brain of patients with Parkinson's disease may, for example, prove useful as a means to replace a defective gene, introduce a potentially neuroprotective or neurorestorative protein, or permit the physiological delivery of a deficient neurotransmitter. Recent observations suggest that the oral administration of currently available dopaminomimetics to relatively advanced parkinsonian patients leads to nonphysiologic intermittent stimulation of striatal neurons that express dopamine receptors. Resultant activation of signal transduction pathways from these dopaminergic receptors on medium-sized GABAergic neurons apparently induces long-term potentiation of adjacent glutamatergic receptors of theN-methyl-d-aspartate subtype. The effects of dopaminergic drugs thus become modified in ways that favor the clinical appearance of response fluctuations and peak-dose dyskinesias. In parkinsonian models as well as in patients with Parkinson's disease, continuous dopaminergic replacement tends to prevent or alleviate these adverse effects. By continuously maintaining appropriate cerebral dopamine concentrations, molecular techniques which stimulate an increase in the intrastriatal activity of tyrosine hydroxylase, the rate-limiting enzyme for dopamine synthesis, might be expected to palliate parkinsonian symptoms with less risk of the disabling consequences of current therapy. Clinical study of these approaches could also serve as initial, relatively simple, proof-of-principle evaluations of the safety and efficacy of genetic approaches to the treatment of basic disease processes in Parkinson's disease and related neurodegenerative disorders.</abstract><qualityIndicators><score>7.563</score><pdfVersion>1.1</pdfVersion><pdfPageSize>554 x 734 pts</pdfPageSize><refBibsNative>true</refBibsNative><keywordCount>0</keywordCount><abstractCharCount>1798</abstractCharCount><pdfWordCount>4803</pdfWordCount><pdfCharCount>32281</pdfCharCount><pdfPageCount>7</pdfPageCount><abstractWordCount>230</abstractWordCount></qualityIndicators><title>Gene Therapy for Parkinson's Disease: An Approach to the Prevention or Palliation of Levodopa-Associated Motor Complications</title><pii><json:string>S0014-4886(96)96388-8</json:string></pii><genre><json:string>research-article</json:string></genre><host><volume>144</volume><pii><json:string>S0014-4886(00)X0059-3</json:string></pii><pages><last>57</last><first>51</first></pages><issn><json:string>0014-4886</json:string></issn><issue>1</issue><genre><json:string>Journal</json:string></genre><language><json:string>unknown</json:string></language><title>Experimental Neurology</title><publicationDate>1997</publicationDate></host><categories><wos><json:string>NEUROSCIENCES</json:string></wos></categories><publicationDate>1997</publicationDate><copyrightDate>1997</copyrightDate><doi><json:string>10.1006/exnr.1996.6388</json:string></doi><id>A157EE11D81693A2773389872E64B081B653E6FD</id><fulltext><json:item><original>true</original><mimetype>application/pdf</mimetype><extension>pdf</extension><uri>https://api.istex.fr/document/A157EE11D81693A2773389872E64B081B653E6FD/fulltext/pdf</uri></json:item><json:item><original>false</original><mimetype>application/zip</mimetype><extension>zip</extension><uri>https://api.istex.fr/document/A157EE11D81693A2773389872E64B081B653E6FD/fulltext/zip</uri></json:item><istex:fulltextTEI uri="https://api.istex.fr/document/A157EE11D81693A2773389872E64B081B653E6FD/fulltext/tei"><teiHeader><fileDesc><titleStmt><title level="a" type="main" xml:lang="en">Gene Therapy for Parkinson's Disease: An Approach to the Prevention or Palliation of Levodopa-Associated Motor Complications</title></titleStmt><publicationStmt><authority>ISTEX</authority><publisher>ELSEVIER</publisher><availability><p>ELSEVIER</p></availability><date>1997</date></publicationStmt><notesStmt><note type="content">Section title: Regular Article</note></notesStmt><sourceDesc><biblStruct type="inbook"><analytic><title level="a" type="main" xml:lang="en">Gene Therapy for Parkinson's Disease: An Approach to the Prevention or Palliation of Levodopa-Associated Motor Complications</title><author><persName><forename type="first">M.Maral</forename><surname>Mouradian</surname></persName><affiliation>Experimental Therapeutics Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland, 20892</affiliation></author><author><persName><forename type="first">Thomas N.</forename><surname>Chase</surname></persName><affiliation>Experimental Therapeutics Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland, 20892</affiliation></author></analytic><monogr><title level="j">Experimental Neurology</title><title level="j" type="abbrev">YEXNR</title><idno type="pISSN">0014-4886</idno><idno type="PII">S0014-4886(00)X0059-3</idno><imprint><publisher>ELSEVIER</publisher><date type="published" when="1997"></date><biblScope unit="volume">144</biblScope><biblScope unit="issue">1</biblScope><biblScope unit="page" from="51">51</biblScope><biblScope unit="page" to="57">57</biblScope></imprint></monogr><idno type="istex">A157EE11D81693A2773389872E64B081B653E6FD</idno><idno type="DOI">10.1006/exnr.1996.6388</idno><idno type="PII">S0014-4886(96)96388-8</idno></biblStruct></sourceDesc></fileDesc><profileDesc><creation><date>1997</date></creation><langUsage><language ident="en">en</language></langUsage><abstract xml:lang="en"><p>Gene therapy holds considerable potential for the treatment of central nervous system disease. The introduction of functional genes into the brain of patients with Parkinson's disease may, for example, prove useful as a means to replace a defective gene, introduce a potentially neuroprotective or neurorestorative protein, or permit the physiological delivery of a deficient neurotransmitter. Recent observations suggest that the oral administration of currently available dopaminomimetics to relatively advanced parkinsonian patients leads to nonphysiologic intermittent stimulation of striatal neurons that express dopamine receptors. Resultant activation of signal transduction pathways from these dopaminergic receptors on medium-sized GABAergic neurons apparently induces long-term potentiation of adjacent glutamatergic receptors of theN-methyl-d-aspartate subtype. The effects of dopaminergic drugs thus become modified in ways that favor the clinical appearance of response fluctuations and peak-dose dyskinesias. In parkinsonian models as well as in patients with Parkinson's disease, continuous dopaminergic replacement tends to prevent or alleviate these adverse effects. By continuously maintaining appropriate cerebral dopamine concentrations, molecular techniques which stimulate an increase in the intrastriatal activity of tyrosine hydroxylase, the rate-limiting enzyme for dopamine synthesis, might be expected to palliate parkinsonian symptoms with less risk of the disabling consequences of current therapy. Clinical study of these approaches could also serve as initial, relatively simple, proof-of-principle evaluations of the safety and efficacy of genetic approaches to the treatment of basic disease processes in Parkinson's disease and related neurodegenerative disorders.</p></abstract></profileDesc><revisionDesc><change when="1997">Published</change></revisionDesc></teiHeader></istex:fulltextTEI><json:item><original>false</original><mimetype>text/plain</mimetype><extension>txt</extension><uri>https://api.istex.fr/document/A157EE11D81693A2773389872E64B081B653E6FD/fulltext/txt</uri></json:item></fulltext><metadata><istex:metadataXml wicri:clean="Elsevier, elements deleted: tail"><istex:xmlDeclaration>version="1.0" encoding="utf-8"</istex:xmlDeclaration><istex:docType PUBLIC="-//ES//DTD journal article DTD version 4.5.2//EN//XML" URI="art452.dtd" name="istex:docType"></istex:docType><istex:document><converted-article version="4.5.2" docsubtype="fla" xml:lang="en"><item-info><jid>YEXNR</jid><aid>96388</aid><ce:pii>S0014-4886(96)96388-8</ce:pii><ce:doi>10.1006/exnr.1996.6388</ce:doi><ce:copyright type="full-transfer" year="1997">Academic Press</ce:copyright></item-info><head><ce:dochead><ce:textfn>Regular Article</ce:textfn></ce:dochead><ce:title>Gene Therapy for Parkinson's Disease: An Approach to the Prevention or Palliation of Levodopa-Associated Motor Complications</ce:title><ce:author-group><ce:author><ce:given-name>M.Maral</ce:given-name><ce:surname>Mouradian</ce:surname></ce:author><ce:author><ce:given-name>Thomas N.</ce:given-name><ce:surname>Chase</ce:surname></ce:author><ce:affiliation><ce:textfn>Experimental Therapeutics Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland, 20892</ce:textfn></ce:affiliation></ce:author-group><ce:abstract><ce:section-title>Abstract</ce:section-title><ce:abstract-sec><ce:simple-para>Gene therapy holds considerable potential for the treatment of central nervous system disease. The introduction of functional genes into the brain of patients with Parkinson's disease may, for example, prove useful as a means to replace a defective gene, introduce a potentially neuroprotective or neurorestorative protein, or permit the physiological delivery of a deficient neurotransmitter. Recent observations suggest that the oral administration of currently available dopaminomimetics to relatively advanced parkinsonian patients leads to nonphysiologic intermittent stimulation of striatal neurons that express dopamine receptors. Resultant activation of signal transduction pathways from these dopaminergic receptors on medium-sized GABAergic neurons apparently induces long-term potentiation of adjacent glutamatergic receptors of the<ce:italic>N</ce:italic>-methyl-<ce:small-caps>d</ce:small-caps>-aspartate subtype. The effects of dopaminergic drugs thus become modified in ways that favor the clinical appearance of response fluctuations and peak-dose dyskinesias. In parkinsonian models as well as in patients with Parkinson's disease, continuous dopaminergic replacement tends to prevent or alleviate these adverse effects. By continuously maintaining appropriate cerebral dopamine concentrations, molecular techniques which stimulate an increase in the intrastriatal activity of tyrosine hydroxylase, the rate-limiting enzyme for dopamine synthesis, might be expected to palliate parkinsonian symptoms with less risk of the disabling consequences of current therapy. Clinical study of these approaches could also serve as initial, relatively simple, proof-of-principle evaluations of the safety and efficacy of genetic approaches to the treatment of basic disease processes in Parkinson's disease and related neurodegenerative disorders.</ce:simple-para></ce:abstract-sec></ce:abstract></head></converted-article></istex:document></istex:metadataXml><mods version="3.6"><titleInfo lang="en"><title>Gene Therapy for Parkinson's Disease: An Approach to the Prevention or Palliation of Levodopa-Associated Motor Complications</title></titleInfo><titleInfo type="alternative" lang="en" contentType="CDATA"><title>Gene Therapy for Parkinson's Disease: An Approach to the Prevention or Palliation of Levodopa-Associated Motor Complications</title></titleInfo><name type="personal"><namePart type="given">M.Maral</namePart><namePart type="family">Mouradian</namePart><affiliation>Experimental Therapeutics Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland, 20892</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Thomas N.</namePart><namePart type="family">Chase</namePart><affiliation>Experimental Therapeutics Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland, 20892</affiliation><role><roleTerm type="text">author</roleTerm></role></name><typeOfResource>text</typeOfResource><genre type="research-article" displayLabel="Full-length article"></genre><originInfo><publisher>ELSEVIER</publisher><dateIssued encoding="w3cdtf">1997</dateIssued><copyrightDate encoding="w3cdtf">1997</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="en">Gene therapy holds considerable potential for the treatment of central nervous system disease. The introduction of functional genes into the brain of patients with Parkinson's disease may, for example, prove useful as a means to replace a defective gene, introduce a potentially neuroprotective or neurorestorative protein, or permit the physiological delivery of a deficient neurotransmitter. Recent observations suggest that the oral administration of currently available dopaminomimetics to relatively advanced parkinsonian patients leads to nonphysiologic intermittent stimulation of striatal neurons that express dopamine receptors. Resultant activation of signal transduction pathways from these dopaminergic receptors on medium-sized GABAergic neurons apparently induces long-term potentiation of adjacent glutamatergic receptors of theN-methyl-d-aspartate subtype. The effects of dopaminergic drugs thus become modified in ways that favor the clinical appearance of response fluctuations and peak-dose dyskinesias. In parkinsonian models as well as in patients with Parkinson's disease, continuous dopaminergic replacement tends to prevent or alleviate these adverse effects. By continuously maintaining appropriate cerebral dopamine concentrations, molecular techniques which stimulate an increase in the intrastriatal activity of tyrosine hydroxylase, the rate-limiting enzyme for dopamine synthesis, might be expected to palliate parkinsonian symptoms with less risk of the disabling consequences of current therapy. Clinical study of these approaches could also serve as initial, relatively simple, proof-of-principle evaluations of the safety and efficacy of genetic approaches to the treatment of basic disease processes in Parkinson's disease and related neurodegenerative disorders.</abstract><note type="content">Section title: Regular Article</note><relatedItem type="host"><titleInfo><title>Experimental Neurology</title></titleInfo><titleInfo type="abbreviated"><title>YEXNR</title></titleInfo><genre type="Journal">journal</genre><originInfo><dateIssued encoding="w3cdtf">199703</dateIssued></originInfo><identifier type="ISSN">0014-4886</identifier><identifier type="PII">S0014-4886(00)X0059-3</identifier><part><date>199703</date><detail type="volume"><number>144</number><caption>vol.</caption></detail><detail type="issue"><number>1</number><caption>no.</caption></detail><extent unit="issue pages"><start>1</start><end>237</end></extent><extent unit="pages"><start>51</start><end>57</end></extent></part></relatedItem><identifier type="istex">A157EE11D81693A2773389872E64B081B653E6FD</identifier><identifier type="DOI">10.1006/exnr.1996.6388</identifier><identifier type="PII">S0014-4886(96)96388-8</identifier><accessCondition type="use and reproduction" contentType="">© 1997Academic Press</accessCondition><recordInfo><recordContentSource>ELSEVIER</recordContentSource><recordOrigin>Academic Press, ©1997</recordOrigin></recordInfo></mods></metadata><enrichments><istex:catWosTEI uri="https://api.istex.fr/document/A157EE11D81693A2773389872E64B081B653E6FD/enrichments/catWos"><teiHeader><profileDesc><textClass><classCode scheme="WOS">NEUROSCIENCES</classCode></textClass></profileDesc></teiHeader></istex:catWosTEI></enrichments><serie></serie></istex></record>Pour manipuler ce document sous Unix (Dilib)
EXPLOR_STEP=$WICRI_ROOT/Wicri/Sante/explor/ParkinsonV1/Data/Main/Corpus
HfdSelect -h $EXPLOR_STEP/biblio.hfd -nk 002019 | SxmlIndent | more
Ou
HfdSelect -h $EXPLOR_AREA/Data/Main/Corpus/biblio.hfd -nk 002019 | SxmlIndent | more
Pour mettre un lien sur cette page dans le réseau Wicri
{{Explor lien
|wiki= Wicri/Sante
|area= ParkinsonV1
|flux= Main
|étape= Corpus
|type= RBID
|clé= ISTEX:A157EE11D81693A2773389872E64B081B653E6FD
|texte= Gene Therapy for Parkinson's Disease: An Approach to the Prevention or Palliation of Levodopa-Associated Motor Complications
}}
| This area was generated with Dilib version V0.6.23. |  |