Viral vector-mediated gene therapy for Parkinson's disease
Identifieur interne : 002423 ( Main/Corpus ); précédent : 002422; suivant : 002424Viral vector-mediated gene therapy for Parkinson's disease
Auteurs : Marina E. Emborg ; Nicole Deglon ; Liza Leventhal ; Patrick Aebischer ; Jeffrey H. KordowerSource :
- Clinical Neuroscience Research [ 1566-2772 ] ; 2001.
English descriptors
Abstract
Parkinson's disease (PD) is a progressive neurodegenerative disorder that affects 1% of the population above the age of 60. The cause of the disease remains unknown. The histopathological hallmarks of the disease are intracytoplasmic Lewy bodies and dopaminergic striatal insufficiency secondary to a loss of dopaminergic neurons in the substantia nigra pars compacta (SN). Pharmacological treatment options for PD are often limited by the ability of prodopaminergic drugs to function within the nigrostriatal system, without activating other dopaminergic, but non-nigrostriatal regions, of the CNS. Even if this obstacle is overcome, considerations regarding the chronic availability of the drug can limit drug utility. Gene delivery systems are ideal for delivering therapeutic molecules to site specific regions of the CNS. Via gene therapy, a piece or pieces of DNA placed into a carrying vector encoding for a substance of interest is introduced into cells. While there are many ways to apply this technology, this review will focus on in vivo gene therapy as it applies to Parkinson's disease. Using stereotaxic surgery, vectors can be introduced into specific target areas in the brain and deliver genes encoding for therapeutic molecules. By delivering genes using gene therapy approaches, a therapeutic molecule can be delivered chronically in a site-specific fashion, diminishing unwanted side effects and repeated interventions to obtain useful levels of the drug. Throughout this review, we discuss the potential for gene delivery aimed at enhancing dopamine production or providing neuroprotection for nigrostriatal neurons to serve as a therapeutic strategy for PD.
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DOI: 10.1016/S1566-2772(01)00027-5
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Emborg</name><affiliation><mods:affiliation>Department of Neurological Sciences, and Research Center for Brain Repair, Rush Presbyterian-St. Luke's Medical Center, 2242 West Harrison Street, Suite 200, Chicago, IL 60612, USA</mods:affiliation></affiliation></author><author><name sortKey="Deglon, Nicole" sort="Deglon, Nicole" uniqKey="Deglon N" first="Nicole" last="Deglon">Nicole Deglon</name><affiliation><mods:affiliation>Division of Surgical Research and Gene Therapy Center, Lausanne University Medical School, Lausanne, Switzerland</mods:affiliation></affiliation></author><author><name sortKey="Leventhal, Liza" sort="Leventhal, Liza" uniqKey="Leventhal L" first="Liza" last="Leventhal">Liza Leventhal</name><affiliation><mods:affiliation>Department of Neurological Sciences, and Research Center for Brain Repair, Rush Presbyterian-St. Luke's Medical Center, 2242 West Harrison Street, Suite 200, Chicago, IL 60612, USA</mods:affiliation></affiliation></author><author><name sortKey="Aebischer, Patrick" sort="Aebischer, Patrick" uniqKey="Aebischer P" first="Patrick" last="Aebischer">Patrick Aebischer</name><affiliation><mods:affiliation>Division of Surgical Research and Gene Therapy Center, Lausanne University Medical School, Lausanne, Switzerland</mods:affiliation></affiliation><affiliation><mods:affiliation>Swiss Federal Institute of Technology Lausanne, EPFL, Lausanne, Switzerland</mods:affiliation></affiliation></author><author><name sortKey="Kordower, Jeffrey H" sort="Kordower, Jeffrey H" uniqKey="Kordower J" first="Jeffrey H." last="Kordower">Jeffrey H. Kordower</name><affiliation><mods:affiliation>Department of Neurological Sciences, and Research Center for Brain Repair, Rush Presbyterian-St. Luke's Medical Center, 2242 West Harrison Street, Suite 200, Chicago, IL 60612, USA</mods:affiliation></affiliation><affiliation><mods:affiliation>Corresponding author. Tel.: +1-312-633-1550; fax: +1-312-633-1564</mods:affiliation></affiliation><affiliation><mods:affiliation>E-mail: jkordowe@rush.edu</mods:affiliation></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">ISTEX</idno><idno type="RBID">ISTEX:EE45D61CD6131F01FA41989956CCDF1B5611A3ED</idno><date when="2001" year="2001">2001</date><idno type="doi">10.1016/S1566-2772(01)00027-5</idno><idno type="url">https://api.istex.fr/document/EE45D61CD6131F01FA41989956CCDF1B5611A3ED/fulltext/pdf</idno><idno type="wicri:Area/Main/Corpus">002423</idno></publicationStmt><sourceDesc><biblStruct><analytic><title level="a" type="main" xml:lang="en">Viral vector-mediated gene therapy for Parkinson's disease</title><author><name sortKey="Emborg, Marina E" sort="Emborg, Marina E" uniqKey="Emborg M" first="Marina E." last="Emborg">Marina E. Emborg</name><affiliation><mods:affiliation>Department of Neurological Sciences, and Research Center for Brain Repair, Rush Presbyterian-St. Luke's Medical Center, 2242 West Harrison Street, Suite 200, Chicago, IL 60612, USA</mods:affiliation></affiliation></author><author><name sortKey="Deglon, Nicole" sort="Deglon, Nicole" uniqKey="Deglon N" first="Nicole" last="Deglon">Nicole Deglon</name><affiliation><mods:affiliation>Division of Surgical Research and Gene Therapy Center, Lausanne University Medical School, Lausanne, Switzerland</mods:affiliation></affiliation></author><author><name sortKey="Leventhal, Liza" sort="Leventhal, Liza" uniqKey="Leventhal L" first="Liza" last="Leventhal">Liza Leventhal</name><affiliation><mods:affiliation>Department of Neurological Sciences, and Research Center for Brain Repair, Rush Presbyterian-St. Luke's Medical Center, 2242 West Harrison Street, Suite 200, Chicago, IL 60612, USA</mods:affiliation></affiliation></author><author><name sortKey="Aebischer, Patrick" sort="Aebischer, Patrick" uniqKey="Aebischer P" first="Patrick" last="Aebischer">Patrick Aebischer</name><affiliation><mods:affiliation>Division of Surgical Research and Gene Therapy Center, Lausanne University Medical School, Lausanne, Switzerland</mods:affiliation></affiliation><affiliation><mods:affiliation>Swiss Federal Institute of Technology Lausanne, EPFL, Lausanne, Switzerland</mods:affiliation></affiliation></author><author><name sortKey="Kordower, Jeffrey H" sort="Kordower, Jeffrey H" uniqKey="Kordower J" first="Jeffrey H." last="Kordower">Jeffrey H. Kordower</name><affiliation><mods:affiliation>Department of Neurological Sciences, and Research Center for Brain Repair, Rush Presbyterian-St. Luke's Medical Center, 2242 West Harrison Street, Suite 200, Chicago, IL 60612, USA</mods:affiliation></affiliation><affiliation><mods:affiliation>Corresponding author. Tel.: +1-312-633-1550; fax: +1-312-633-1564</mods:affiliation></affiliation><affiliation><mods:affiliation>E-mail: jkordowe@rush.edu</mods:affiliation></affiliation></author></analytic><monogr></monogr><series><title level="j">Clinical Neuroscience Research</title><title level="j" type="abbrev">CLIRES</title><idno type="ISSN">1566-2772</idno><imprint><publisher>ELSEVIER</publisher><date type="published" when="2001">2001</date><biblScope unit="volume">1</biblScope><biblScope unit="issue">6</biblScope><biblScope unit="page" from="496">496</biblScope><biblScope unit="page" to="506">506</biblScope></imprint><idno type="ISSN">1566-2772</idno></series><idno type="istex">EE45D61CD6131F01FA41989956CCDF1B5611A3ED</idno><idno type="DOI">10.1016/S1566-2772(01)00027-5</idno><idno type="PII">S1566-2772(01)00027-5</idno></biblStruct></sourceDesc><seriesStmt><idno type="ISSN">1566-2772</idno></seriesStmt></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Dopamine</term><term>Gene therapy</term><term>Glial cell derived neurotrophic factor</term><term>Parkinson's disease</term></keywords></textClass><langUsage><language ident="en">en</language></langUsage></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Parkinson's disease (PD) is a progressive neurodegenerative disorder that affects 1% of the population above the age of 60. The cause of the disease remains unknown. The histopathological hallmarks of the disease are intracytoplasmic Lewy bodies and dopaminergic striatal insufficiency secondary to a loss of dopaminergic neurons in the substantia nigra pars compacta (SN). Pharmacological treatment options for PD are often limited by the ability of prodopaminergic drugs to function within the nigrostriatal system, without activating other dopaminergic, but non-nigrostriatal regions, of the CNS. Even if this obstacle is overcome, considerations regarding the chronic availability of the drug can limit drug utility. Gene delivery systems are ideal for delivering therapeutic molecules to site specific regions of the CNS. Via gene therapy, a piece or pieces of DNA placed into a carrying vector encoding for a substance of interest is introduced into cells. While there are many ways to apply this technology, this review will focus on in vivo gene therapy as it applies to Parkinson's disease. Using stereotaxic surgery, vectors can be introduced into specific target areas in the brain and deliver genes encoding for therapeutic molecules. By delivering genes using gene therapy approaches, a therapeutic molecule can be delivered chronically in a site-specific fashion, diminishing unwanted side effects and repeated interventions to obtain useful levels of the drug. Throughout this review, we discuss the potential for gene delivery aimed at enhancing dopamine production or providing neuroprotection for nigrostriatal neurons to serve as a therapeutic strategy for PD.</div></front></TEI><istex><corpusName>elsevier</corpusName><author><json:item><name>Marina E. Emborg</name><affiliations><json:string>Department of Neurological Sciences, and Research Center for Brain Repair, Rush Presbyterian-St. Luke's Medical Center, 2242 West Harrison Street, Suite 200, Chicago, IL 60612, USA</json:string></affiliations></json:item><json:item><name>Nicole Deglon</name><affiliations><json:string>Division of Surgical Research and Gene Therapy Center, Lausanne University Medical School, Lausanne, Switzerland</json:string></affiliations></json:item><json:item><name>Liza Leventhal</name><affiliations><json:string>Department of Neurological Sciences, and Research Center for Brain Repair, Rush Presbyterian-St. Luke's Medical Center, 2242 West Harrison Street, Suite 200, Chicago, IL 60612, USA</json:string></affiliations></json:item><json:item><name>Patrick Aebischer</name><affiliations><json:string>Division of Surgical Research and Gene Therapy Center, Lausanne University Medical School, Lausanne, Switzerland</json:string><json:string>Swiss Federal Institute of Technology Lausanne, EPFL, Lausanne, Switzerland</json:string></affiliations></json:item><json:item><name>Jeffrey H. Kordower</name><affiliations><json:string>Department of Neurological Sciences, and Research Center for Brain Repair, Rush Presbyterian-St. Luke's Medical Center, 2242 West Harrison Street, Suite 200, Chicago, IL 60612, USA</json:string><json:string>Corresponding author. Tel.: +1-312-633-1550; fax: +1-312-633-1564</json:string><json:string>E-mail: jkordowe@rush.edu</json:string></affiliations></json:item></author><subject><json:item><lang><json:string>eng</json:string></lang><value>Gene therapy</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>Parkinson's disease</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>Dopamine</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>Glial cell derived neurotrophic factor</value></json:item></subject><language><json:string>eng</json:string></language><abstract>Parkinson's disease (PD) is a progressive neurodegenerative disorder that affects 1% of the population above the age of 60. The cause of the disease remains unknown. The histopathological hallmarks of the disease are intracytoplasmic Lewy bodies and dopaminergic striatal insufficiency secondary to a loss of dopaminergic neurons in the substantia nigra pars compacta (SN). Pharmacological treatment options for PD are often limited by the ability of prodopaminergic drugs to function within the nigrostriatal system, without activating other dopaminergic, but non-nigrostriatal regions, of the CNS. Even if this obstacle is overcome, considerations regarding the chronic availability of the drug can limit drug utility. Gene delivery systems are ideal for delivering therapeutic molecules to site specific regions of the CNS. Via gene therapy, a piece or pieces of DNA placed into a carrying vector encoding for a substance of interest is introduced into cells. While there are many ways to apply this technology, this review will focus on in vivo gene therapy as it applies to Parkinson's disease. Using stereotaxic surgery, vectors can be introduced into specific target areas in the brain and deliver genes encoding for therapeutic molecules. By delivering genes using gene therapy approaches, a therapeutic molecule can be delivered chronically in a site-specific fashion, diminishing unwanted side effects and repeated interventions to obtain useful levels of the drug. Throughout this review, we discuss the potential for gene delivery aimed at enhancing dopamine production or providing neuroprotection for nigrostriatal neurons to serve as a therapeutic strategy for PD.</abstract><qualityIndicators><score>7.976</score><pdfVersion>1.2</pdfVersion><pdfPageSize>595 x 794 pts</pdfPageSize><refBibsNative>true</refBibsNative><keywordCount>4</keywordCount><abstractCharCount>1679</abstractCharCount><pdfWordCount>6772</pdfWordCount><pdfCharCount>44417</pdfCharCount><pdfPageCount>11</pdfPageCount><abstractWordCount>248</abstractWordCount></qualityIndicators><title>Viral vector-mediated gene therapy for Parkinson's disease</title><pii><json:string>S1566-2772(01)00027-5</json:string></pii><genre><json:string>review-article</json:string></genre><host><volume>1</volume><pii><json:string>S1566-2772(00)X0005-9</json:string></pii><pages><last>506</last><first>496</first></pages><issn><json:string>1566-2772</json:string></issn><issue>6</issue><genre><json:string>Journal</json:string></genre><language><json:string>unknown</json:string></language><title>Clinical Neuroscience Research</title><publicationDate>2001</publicationDate></host><categories><wos><json:string>CLINICAL NEUROLOGY</json:string><json:string>NEUROSCIENCES</json:string></wos></categories><publicationDate>2001</publicationDate><copyrightDate>2001</copyrightDate><doi><json:string>10.1016/S1566-2772(01)00027-5</json:string></doi><id>EE45D61CD6131F01FA41989956CCDF1B5611A3ED</id><fulltext><json:item><original>true</original><mimetype>application/pdf</mimetype><extension>pdf</extension><uri>https://api.istex.fr/document/EE45D61CD6131F01FA41989956CCDF1B5611A3ED/fulltext/pdf</uri></json:item><json:item><original>true</original><mimetype>text/plain</mimetype><extension>txt</extension><uri>https://api.istex.fr/document/EE45D61CD6131F01FA41989956CCDF1B5611A3ED/fulltext/txt</uri></json:item><json:item><original>false</original><mimetype>application/zip</mimetype><extension>zip</extension><uri>https://api.istex.fr/document/EE45D61CD6131F01FA41989956CCDF1B5611A3ED/fulltext/zip</uri></json:item><istex:fulltextTEI uri="https://api.istex.fr/document/EE45D61CD6131F01FA41989956CCDF1B5611A3ED/fulltext/tei"><teiHeader><fileDesc><titleStmt><title level="a" type="main" xml:lang="en">Viral vector-mediated gene therapy for Parkinson's disease</title></titleStmt><publicationStmt><authority>ISTEX</authority><publisher>ELSEVIER</publisher><availability><p>ELSEVIER</p></availability><date>2001</date></publicationStmt><notesStmt><note type="content">Fig. 1: (A) A robust increase in TH-ir was present in the right caudate nucleus and putamen following injections of intrastriatal Lenti-GDNF in aged Rhesus. (B) Less intense staining for TH was observed bilaterally in aged monkeys receiving injections of Lenti-βgal. (C) Lenti-GDNF-treated monkeys also exhibited an increase in the number and volume of TH-positive neurons in the substantia nigra compared to (D) Lenti-βgal-treated cohorts. (E) Lenti-GDNF-treated monkeys also displayed increases in TH-mRNA within individual nigral neurons compared to (F) Lenti-βgal-treated controls. Scale bar in (F) represents 4500 μm for panels (A) and (B), 250 μm for panels (C) and (D), 100 μm for panels (E) and (F). Reprinted with permission from: Kordower et al., Science 2000;290:767-772. Copyright 2000, American Association for the Advancement of Science.</note><note type="content">Fig. 2: Lenti-GDNF-treated monkeys displayed functional improvements after MPTP on (A) the clinical rating scale and (B) the fine motor skill task. *P<0.005 vs lenti-βGal-treated monkeys. Reprinted with permission from: Kordower et al., Science 2000;290:767-772. Copyright 2000 American Association for the Advancement of Science.</note><note type="content">Fig. 3: Low power dark-field photomicrographs through the right striatum (A,B) and sunbstantia nigra (B,C) of TH-immunostained sections of MPTP-treated monkeys treated with (A,C) lenti-βgal-treated or (B,D) lenti-GDNF-treated. Reprinted with permission from: Kordower et al., Science 2000;290:767-772. Copyright 2000 American Association for the Advancement of Science.</note><note type="content">Fig. 4: Robust GDNF immunoreactivity was seen in the right caudate (A), right putamen (B), and left ventral midbrain (C) 8 months post lenti-GDNF treatment. (D,E) In the right substantia nigra, many GDNF-immunoreactive neurons were seen. This labeling represents retrograde transport of GDNF after injections of lenti-GDNF into the right striatum. Reprinted with permission from: Kordower et al., Science 2000;290:767-772. Copyright 2000 American Association for the Advancement of Science.</note></notesStmt><sourceDesc><biblStruct type="inbook"><analytic><title level="a" type="main" xml:lang="en">Viral vector-mediated gene therapy for Parkinson's disease</title><author><persName><forename type="first">Marina E.</forename><surname>Emborg</surname></persName><affiliation>Department of Neurological Sciences, and Research Center for Brain Repair, Rush Presbyterian-St. Luke's Medical Center, 2242 West Harrison Street, Suite 200, Chicago, IL 60612, USA</affiliation></author><author><persName><forename type="first">Nicole</forename><surname>Deglon</surname></persName><affiliation>Division of Surgical Research and Gene Therapy Center, Lausanne University Medical School, Lausanne, Switzerland</affiliation></author><author><persName><forename type="first">Liza</forename><surname>Leventhal</surname></persName><affiliation>Department of Neurological Sciences, and Research Center for Brain Repair, Rush Presbyterian-St. Luke's Medical Center, 2242 West Harrison Street, Suite 200, Chicago, IL 60612, USA</affiliation></author><author><persName><forename type="first">Patrick</forename><surname>Aebischer</surname></persName><affiliation>Division of Surgical Research and Gene Therapy Center, Lausanne University Medical School, Lausanne, Switzerland</affiliation><affiliation>Swiss Federal Institute of Technology Lausanne, EPFL, Lausanne, Switzerland</affiliation></author><author><persName><forename type="first">Jeffrey H.</forename><surname>Kordower</surname></persName><email>jkordowe@rush.edu</email><affiliation>Department of Neurological Sciences, and Research Center for Brain Repair, Rush Presbyterian-St. Luke's Medical Center, 2242 West Harrison Street, Suite 200, Chicago, IL 60612, USA</affiliation><affiliation>Corresponding author. Tel.: +1-312-633-1550; fax: +1-312-633-1564</affiliation></author></analytic><monogr><title level="j">Clinical Neuroscience Research</title><title level="j" type="abbrev">CLIRES</title><idno type="pISSN">1566-2772</idno><idno type="PII">S1566-2772(00)X0005-9</idno><imprint><publisher>ELSEVIER</publisher><date type="published" when="2001"></date><biblScope unit="volume">1</biblScope><biblScope unit="issue">6</biblScope><biblScope unit="page" from="496">496</biblScope><biblScope unit="page" to="506">506</biblScope></imprint></monogr><idno type="istex">EE45D61CD6131F01FA41989956CCDF1B5611A3ED</idno><idno type="DOI">10.1016/S1566-2772(01)00027-5</idno><idno type="PII">S1566-2772(01)00027-5</idno></biblStruct></sourceDesc></fileDesc><profileDesc><creation><date>2001</date></creation><langUsage><language ident="en">en</language></langUsage><abstract xml:lang="en"><p>Parkinson's disease (PD) is a progressive neurodegenerative disorder that affects 1% of the population above the age of 60. The cause of the disease remains unknown. The histopathological hallmarks of the disease are intracytoplasmic Lewy bodies and dopaminergic striatal insufficiency secondary to a loss of dopaminergic neurons in the substantia nigra pars compacta (SN). Pharmacological treatment options for PD are often limited by the ability of prodopaminergic drugs to function within the nigrostriatal system, without activating other dopaminergic, but non-nigrostriatal regions, of the CNS. Even if this obstacle is overcome, considerations regarding the chronic availability of the drug can limit drug utility. Gene delivery systems are ideal for delivering therapeutic molecules to site specific regions of the CNS. Via gene therapy, a piece or pieces of DNA placed into a carrying vector encoding for a substance of interest is introduced into cells. While there are many ways to apply this technology, this review will focus on in vivo gene therapy as it applies to Parkinson's disease. Using stereotaxic surgery, vectors can be introduced into specific target areas in the brain and deliver genes encoding for therapeutic molecules. By delivering genes using gene therapy approaches, a therapeutic molecule can be delivered chronically in a site-specific fashion, diminishing unwanted side effects and repeated interventions to obtain useful levels of the drug. Throughout this review, we discuss the potential for gene delivery aimed at enhancing dopamine production or providing neuroprotection for nigrostriatal neurons to serve as a therapeutic strategy for PD.</p></abstract><textClass xml:lang="en"><keywords scheme="keyword"><list><head>Keywords</head><item><term>Gene therapy</term></item><item><term>Parkinson's disease</term></item><item><term>Dopamine</term></item><item><term>Glial cell derived neurotrophic factor</term></item></list></keywords></textClass></profileDesc><revisionDesc><change when="2001-08-20">Registration</change><change when="2001-08-09">Modified</change><change when="2001">Published</change></revisionDesc></teiHeader></istex:fulltextTEI></fulltext><metadata><istex:metadataXml wicri:clean="Elsevier, elements deleted: ce:floats; body; 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:entity SYSTEM="gr1" NDATA="IMAGE" name="gr1"></istex:entity><istex:entity SYSTEM="gr2" NDATA="IMAGE" name="gr2"></istex:entity><istex:entity SYSTEM="gr3" NDATA="IMAGE" name="gr3"></istex:entity><istex:entity SYSTEM="gr4" NDATA="IMAGE" name="gr4"></istex:entity></istex:docType><istex:document><converted-article version="4.5.2" docsubtype="rev" xml:lang="en"><item-info><jid>CLIRES</jid><aid>49</aid><ce:pii>S1566-2772(01)00027-5</ce:pii><ce:doi>10.1016/S1566-2772(01)00027-5</ce:doi><ce:copyright type="full-transfer" year="2001">Elsevier Science B.V.</ce:copyright></item-info><head><ce:title>Viral vector-mediated gene therapy for Parkinson's disease</ce:title><ce:author-group><ce:author><ce:given-name>Marina E.</ce:given-name><ce:surname>Emborg</ce:surname><ce:cross-ref refid="AFF1"><ce:sup>a</ce:sup></ce:cross-ref></ce:author><ce:author><ce:given-name>Nicole</ce:given-name><ce:surname>Deglon</ce:surname><ce:cross-ref refid="AFF2"><ce:sup>b</ce:sup></ce:cross-ref></ce:author><ce:author><ce:given-name>Liza</ce:given-name><ce:surname>Leventhal</ce:surname><ce:cross-ref refid="AFF1"><ce:sup>a</ce:sup></ce:cross-ref></ce:author><ce:author><ce:given-name>Patrick</ce:given-name><ce:surname>Aebischer</ce:surname><ce:cross-ref refid="AFF2"><ce:sup>b</ce:sup></ce:cross-ref><ce:cross-ref refid="AFF3"><ce:sup>c</ce:sup></ce:cross-ref></ce:author><ce:author><ce:given-name>Jeffrey H.</ce:given-name><ce:surname>Kordower</ce:surname><ce:cross-ref refid="AFF1"><ce:sup>a</ce:sup></ce:cross-ref><ce:cross-ref refid="COR1"><ce:sup>∗</ce:sup></ce:cross-ref><ce:e-address>jkordowe@rush.edu</ce:e-address></ce:author><ce:affiliation id="AFF1"><ce:label>a</ce:label><ce:textfn>Department of Neurological Sciences, and Research Center for Brain Repair, Rush Presbyterian-St. Luke's Medical Center, 2242 West Harrison Street, Suite 200, Chicago, IL 60612, USA</ce:textfn></ce:affiliation><ce:affiliation id="AFF2"><ce:label>b</ce:label><ce:textfn>Division of Surgical Research and Gene Therapy Center, Lausanne University Medical School, Lausanne, Switzerland</ce:textfn></ce:affiliation><ce:affiliation id="AFF3"><ce:label>c</ce:label><ce:textfn>Swiss Federal Institute of Technology Lausanne, EPFL, Lausanne, Switzerland</ce:textfn></ce:affiliation><ce:correspondence id="COR1"><ce:label>∗</ce:label><ce:text>Corresponding author. Tel.: +1-312-633-1550; fax: +1-312-633-1564</ce:text></ce:correspondence></ce:author-group><ce:date-received day="3" month="8" year="2001"></ce:date-received><ce:date-revised day="9" month="8" year="2001"></ce:date-revised><ce:date-accepted day="20" month="8" year="2001"></ce:date-accepted><ce:abstract><ce:section-title>Abstract</ce:section-title><ce:abstract-sec><ce:simple-para>Parkinson's disease (PD) is a progressive neurodegenerative disorder that affects 1% of the population above the age of 60. The cause of the disease remains unknown. The histopathological hallmarks of the disease are intracytoplasmic Lewy bodies and dopaminergic striatal insufficiency secondary to a loss of dopaminergic neurons in the substantia nigra pars compacta (SN). Pharmacological treatment options for PD are often limited by the ability of prodopaminergic drugs to function within the nigrostriatal system, without activating other dopaminergic, but non-nigrostriatal regions, of the CNS. Even if this obstacle is overcome, considerations regarding the chronic availability of the drug can limit drug utility. Gene delivery systems are ideal for delivering therapeutic molecules to site specific regions of the CNS. Via gene therapy, a piece or pieces of DNA placed into a carrying vector encoding for a substance of interest is introduced into cells. While there are many ways to apply this technology, this review will focus on in vivo gene therapy as it applies to Parkinson's disease. Using stereotaxic surgery, vectors can be introduced into specific target areas in the brain and deliver genes encoding for therapeutic molecules. By delivering genes using gene therapy approaches, a therapeutic molecule can be delivered chronically in a site-specific fashion, diminishing unwanted side effects and repeated interventions to obtain useful levels of the drug. Throughout this review, we discuss the potential for gene delivery aimed at enhancing dopamine production or providing neuroprotection for nigrostriatal neurons to serve as a therapeutic strategy for PD.</ce:simple-para></ce:abstract-sec></ce:abstract><ce:keywords class="keyword" xml:lang="en"><ce:section-title>Keywords</ce:section-title><ce:keyword><ce:text>Gene therapy</ce:text></ce:keyword><ce:keyword><ce:text>Parkinson's disease</ce:text></ce:keyword><ce:keyword><ce:text>Dopamine</ce:text></ce:keyword><ce:keyword><ce:text>Glial cell derived neurotrophic factor</ce:text></ce:keyword></ce:keywords></head></converted-article></istex:document></istex:metadataXml><mods version="3.6"><titleInfo lang="en"><title>Viral vector-mediated gene therapy for Parkinson's disease</title></titleInfo><titleInfo type="alternative" lang="en" contentType="CDATA"><title>Viral vector-mediated gene therapy for Parkinson's disease</title></titleInfo><name type="personal"><namePart type="given">Marina E.</namePart><namePart type="family">Emborg</namePart><affiliation>Department of Neurological Sciences, and Research Center for Brain Repair, Rush Presbyterian-St. Luke's Medical Center, 2242 West Harrison Street, Suite 200, Chicago, IL 60612, USA</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Nicole</namePart><namePart type="family">Deglon</namePart><affiliation>Division of Surgical Research and Gene Therapy Center, Lausanne University Medical School, Lausanne, Switzerland</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Liza</namePart><namePart type="family">Leventhal</namePart><affiliation>Department of Neurological Sciences, and Research Center for Brain Repair, Rush Presbyterian-St. Luke's Medical Center, 2242 West Harrison Street, Suite 200, Chicago, IL 60612, USA</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Patrick</namePart><namePart type="family">Aebischer</namePart><affiliation>Division of Surgical Research and Gene Therapy Center, Lausanne University Medical School, Lausanne, Switzerland</affiliation><affiliation>Swiss Federal Institute of Technology Lausanne, EPFL, Lausanne, Switzerland</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Jeffrey H.</namePart><namePart type="family">Kordower</namePart><affiliation>Department of Neurological Sciences, and Research Center for Brain Repair, Rush Presbyterian-St. Luke's Medical Center, 2242 West Harrison Street, Suite 200, Chicago, IL 60612, USA</affiliation><affiliation>Corresponding author. Tel.: +1-312-633-1550; fax: +1-312-633-1564</affiliation><affiliation>E-mail: jkordowe@rush.edu</affiliation><role><roleTerm type="text">author</roleTerm></role></name><typeOfResource>text</typeOfResource><genre type="review-article" displayLabel="Review article"></genre><originInfo><publisher>ELSEVIER</publisher><dateIssued encoding="w3cdtf">2001</dateIssued><dateValid encoding="w3cdtf">2001-08-20</dateValid><dateModified encoding="w3cdtf">2001-08-09</dateModified><copyrightDate encoding="w3cdtf">2001</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">Parkinson's disease (PD) is a progressive neurodegenerative disorder that affects 1% of the population above the age of 60. The cause of the disease remains unknown. The histopathological hallmarks of the disease are intracytoplasmic Lewy bodies and dopaminergic striatal insufficiency secondary to a loss of dopaminergic neurons in the substantia nigra pars compacta (SN). Pharmacological treatment options for PD are often limited by the ability of prodopaminergic drugs to function within the nigrostriatal system, without activating other dopaminergic, but non-nigrostriatal regions, of the CNS. Even if this obstacle is overcome, considerations regarding the chronic availability of the drug can limit drug utility. Gene delivery systems are ideal for delivering therapeutic molecules to site specific regions of the CNS. Via gene therapy, a piece or pieces of DNA placed into a carrying vector encoding for a substance of interest is introduced into cells. While there are many ways to apply this technology, this review will focus on in vivo gene therapy as it applies to Parkinson's disease. Using stereotaxic surgery, vectors can be introduced into specific target areas in the brain and deliver genes encoding for therapeutic molecules. By delivering genes using gene therapy approaches, a therapeutic molecule can be delivered chronically in a site-specific fashion, diminishing unwanted side effects and repeated interventions to obtain useful levels of the drug. Throughout this review, we discuss the potential for gene delivery aimed at enhancing dopamine production or providing neuroprotection for nigrostriatal neurons to serve as a therapeutic strategy for PD.</abstract><note type="content">Fig. 1: (A) A robust increase in TH-ir was present in the right caudate nucleus and putamen following injections of intrastriatal Lenti-GDNF in aged Rhesus. (B) Less intense staining for TH was observed bilaterally in aged monkeys receiving injections of Lenti-βgal. (C) Lenti-GDNF-treated monkeys also exhibited an increase in the number and volume of TH-positive neurons in the substantia nigra compared to (D) Lenti-βgal-treated cohorts. (E) Lenti-GDNF-treated monkeys also displayed increases in TH-mRNA within individual nigral neurons compared to (F) Lenti-βgal-treated controls. Scale bar in (F) represents 4500 μm for panels (A) and (B), 250 μm for panels (C) and (D), 100 μm for panels (E) and (F). Reprinted with permission from: Kordower et al., Science 2000;290:767-772. Copyright 2000, American Association for the Advancement of Science.</note><note type="content">Fig. 2: Lenti-GDNF-treated monkeys displayed functional improvements after MPTP on (A) the clinical rating scale and (B) the fine motor skill task. *P<0.005 vs lenti-βGal-treated monkeys. Reprinted with permission from: Kordower et al., Science 2000;290:767-772. Copyright 2000 American Association for the Advancement of Science.</note><note type="content">Fig. 3: Low power dark-field photomicrographs through the right striatum (A,B) and sunbstantia nigra (B,C) of TH-immunostained sections of MPTP-treated monkeys treated with (A,C) lenti-βgal-treated or (B,D) lenti-GDNF-treated. Reprinted with permission from: Kordower et al., Science 2000;290:767-772. Copyright 2000 American Association for the Advancement of Science.</note><note type="content">Fig. 4: Robust GDNF immunoreactivity was seen in the right caudate (A), right putamen (B), and left ventral midbrain (C) 8 months post lenti-GDNF treatment. (D,E) In the right substantia nigra, many GDNF-immunoreactive neurons were seen. This labeling represents retrograde transport of GDNF after injections of lenti-GDNF into the right striatum. Reprinted with permission from: Kordower et al., Science 2000;290:767-772. Copyright 2000 American Association for the Advancement of Science.</note><subject lang="en"><genre>Keywords</genre><topic>Gene therapy</topic><topic>Parkinson's disease</topic><topic>Dopamine</topic><topic>Glial cell derived neurotrophic factor</topic></subject><relatedItem type="host"><titleInfo><title>Clinical Neuroscience Research</title></titleInfo><titleInfo type="abbreviated"><title>CLIRES</title></titleInfo><genre type="Journal">journal</genre><originInfo><dateIssued encoding="w3cdtf">200112</dateIssued></originInfo><identifier type="ISSN">1566-2772</identifier><identifier type="PII">S1566-2772(00)X0005-9</identifier><part><date>200112</date><detail type="issue"><title>Advances in Parkinson's Disease Research</title></detail><detail type="volume"><number>1</number><caption>vol.</caption></detail><detail type="issue"><number>6</number><caption>no.</caption></detail><extent unit="issue pages"><start>405</start><end>540</end></extent><extent unit="pages"><start>496</start><end>506</end></extent></part></relatedItem><identifier type="istex">EE45D61CD6131F01FA41989956CCDF1B5611A3ED</identifier><identifier type="DOI">10.1016/S1566-2772(01)00027-5</identifier><identifier type="PII">S1566-2772(01)00027-5</identifier><accessCondition type="use and reproduction" contentType="">© 2001Elsevier Science B.V.</accessCondition><recordInfo><recordContentSource>ELSEVIER</recordContentSource><recordOrigin>Elsevier Science B.V., ©2001</recordOrigin></recordInfo></mods></metadata><enrichments><istex:catWosTEI uri="https://api.istex.fr/document/EE45D61CD6131F01FA41989956CCDF1B5611A3ED/enrichments/catWos"><teiHeader><profileDesc><textClass><classCode scheme="WOS">CLINICAL NEUROLOGY</classCode><classCode scheme="WOS">NEUROSCIENCES</classCode></textClass></profileDesc></teiHeader></istex:catWosTEI></enrichments><serie></serie></istex></record>Pour manipuler ce document sous Unix (Dilib)
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