Dopamine gene therapy for Parkinson's disease in a nonhuman primate without associated dyskinesia.
Identifieur interne : 000B27 ( PubMed/Checkpoint ); précédent : 000B26; suivant : 000B28Dopamine gene therapy for Parkinson's disease in a nonhuman primate without associated dyskinesia.
Auteurs : Béchir Jarraya [France] ; Sabrina Boulet ; G Scott Ralph ; Caroline Jan ; Gilles Bonvento ; Mimoun Azzouz ; James E. Miskin ; Masahiro Shin ; Thierry Delzescaux ; Xavier Drouot ; Anne-Sophie Hérard ; Denise M. Day ; Emmanuel Brouillet ; Susan M. Kingsman ; Philippe Hantraye ; Kyriacos A. Mitrophanous ; Nicholas D. Mazarakis ; Stéphane PalfiSource :
- Science translational medicine [ 1946-6242 ] ; 2009.
English descriptors
- KwdEn :
- MESH :
- chemical , deficiency : Dopamine.
- chemical , genetics : Dopamine.
- complications : Dyskinesias, Parkinson Disease.
- genetics : Lentivirus, Motor Activity.
- therapy : Parkinson Disease.
- Animals, Disease Models, Animal, Genetic Therapy, Genetic Vectors, Macaca mulatta.
Abstract
In Parkinson's disease, degeneration of specific neurons in the midbrain can cause severe motor deficits, including tremors and the inability to initiate movement. The standard treatment is administration of pharmacological agents that transiently increase concentrations of brain dopamine and thereby discontinuously modulate neuronal activity in the striatum, the primary target of dopaminergic neurons. The resulting intermittent dopamine alleviates parkinsonian symptoms but is also thought to cause abnormal involuntary movements, called dyskinesias. To investigate gene therapy for Parkinson's disease, we simulated the disease in macaque monkeys by treating them with the complex I mitochondrial inhibitor 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine, which induces selective degeneration of dopamine-producing neurons. In this model, we demonstrated that injection of a tricistronic lentiviral vector encoding the critical genes for dopamine synthesis (tyrosine hydroxylase, aromatic L-amino acid decarboxylase, and guanosine 5'-triphosphate cyclohydrolase 1) into the striatum safely restored extracellular concentrations of dopamine and corrected the motor deficits for 12 months without associated dyskinesias. Gene therapy-mediated dopamine replacement may be able to correct Parkinsonism in patients without the complications of dyskinesias.
DOI: 10.1126/scitranslmed.3000130
PubMed: 20368163
Affiliations:
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Miskin</name></author><author><name sortKey="Shin, Masahiro" sort="Shin, Masahiro" uniqKey="Shin M" first="Masahiro" last="Shin">Masahiro Shin</name></author><author><name sortKey="Delzescaux, Thierry" sort="Delzescaux, Thierry" uniqKey="Delzescaux T" first="Thierry" last="Delzescaux">Thierry Delzescaux</name></author><author><name sortKey="Drouot, Xavier" sort="Drouot, Xavier" uniqKey="Drouot X" first="Xavier" last="Drouot">Xavier Drouot</name></author><author><name sortKey="Herard, Anne Sophie" sort="Herard, Anne Sophie" uniqKey="Herard A" first="Anne-Sophie" last="Hérard">Anne-Sophie Hérard</name></author><author><name sortKey="Day, Denise M" sort="Day, Denise M" uniqKey="Day D" first="Denise M" last="Day">Denise M. Day</name></author><author><name sortKey="Brouillet, Emmanuel" sort="Brouillet, Emmanuel" uniqKey="Brouillet E" first="Emmanuel" last="Brouillet">Emmanuel Brouillet</name></author><author><name sortKey="Kingsman, Susan M" sort="Kingsman, Susan M" uniqKey="Kingsman S" first="Susan M" last="Kingsman">Susan M. Kingsman</name></author><author><name sortKey="Hantraye, Philippe" sort="Hantraye, Philippe" uniqKey="Hantraye P" first="Philippe" last="Hantraye">Philippe Hantraye</name></author><author><name sortKey="Mitrophanous, Kyriacos A" sort="Mitrophanous, Kyriacos A" uniqKey="Mitrophanous K" first="Kyriacos A" last="Mitrophanous">Kyriacos A. Mitrophanous</name></author><author><name sortKey="Mazarakis, Nicholas D" sort="Mazarakis, Nicholas D" uniqKey="Mazarakis N" first="Nicholas D" last="Mazarakis">Nicholas D. Mazarakis</name></author><author><name sortKey="Palfi, Stephane" sort="Palfi, Stephane" uniqKey="Palfi S" first="Stéphane" last="Palfi">Stéphane Palfi</name></author></analytic><series><title level="j">Science translational medicine</title><idno type="eISSN">1946-6242</idno><imprint><date when="2009" type="published">2009</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Animals</term><term>Disease Models, Animal</term><term>Dopamine (deficiency)</term><term>Dopamine (genetics)</term><term>Dyskinesias (complications)</term><term>Genetic Therapy</term><term>Genetic Vectors</term><term>Lentivirus (genetics)</term><term>Macaca mulatta</term><term>Motor Activity (genetics)</term><term>Parkinson Disease (complications)</term><term>Parkinson Disease (therapy)</term></keywords><keywords scheme="MESH" type="chemical" qualifier="deficiency" xml:lang="en"><term>Dopamine</term></keywords><keywords scheme="MESH" type="chemical" qualifier="genetics" xml:lang="en"><term>Dopamine</term></keywords><keywords scheme="MESH" qualifier="complications" xml:lang="en"><term>Dyskinesias</term><term>Parkinson Disease</term></keywords><keywords scheme="MESH" qualifier="genetics" xml:lang="en"><term>Lentivirus</term><term>Motor Activity</term></keywords><keywords scheme="MESH" qualifier="therapy" xml:lang="en"><term>Parkinson Disease</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Animals</term><term>Disease Models, Animal</term><term>Genetic Therapy</term><term>Genetic Vectors</term><term>Macaca mulatta</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">In Parkinson's disease, degeneration of specific neurons in the midbrain can cause severe motor deficits, including tremors and the inability to initiate movement. The standard treatment is administration of pharmacological agents that transiently increase concentrations of brain dopamine and thereby discontinuously modulate neuronal activity in the striatum, the primary target of dopaminergic neurons. The resulting intermittent dopamine alleviates parkinsonian symptoms but is also thought to cause abnormal involuntary movements, called dyskinesias. To investigate gene therapy for Parkinson's disease, we simulated the disease in macaque monkeys by treating them with the complex I mitochondrial inhibitor 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine, which induces selective degeneration of dopamine-producing neurons. In this model, we demonstrated that injection of a tricistronic lentiviral vector encoding the critical genes for dopamine synthesis (tyrosine hydroxylase, aromatic L-amino acid decarboxylase, and guanosine 5'-triphosphate cyclohydrolase 1) into the striatum safely restored extracellular concentrations of dopamine and corrected the motor deficits for 12 months without associated dyskinesias. Gene therapy-mediated dopamine replacement may be able to correct Parkinsonism in patients without the complications of dyskinesias.</div></front></TEI><pubmed><MedlineCitation Status="MEDLINE" Owner="NLM"><PMID Version="1">20368163</PMID><DateCreated><Year>2010</Year><Month>04</Month><Day>06</Day></DateCreated><DateCompleted><Year>2010</Year><Month>07</Month><Day>12</Day></DateCompleted><DateRevised><Year>2013</Year><Month>11</Month><Day>21</Day></DateRevised><Article PubModel="Print"><Journal><ISSN IssnType="Electronic">1946-6242</ISSN><JournalIssue CitedMedium="Internet"><Volume>1</Volume><Issue>2</Issue><PubDate><Year>2009</Year><Month>Oct</Month><Day>14</Day></PubDate></JournalIssue><Title>Science translational medicine</Title><ISOAbbreviation>Sci Transl Med</ISOAbbreviation></Journal><ArticleTitle>Dopamine gene therapy for Parkinson's disease in a nonhuman primate without associated dyskinesia.</ArticleTitle><Pagination><MedlinePgn>2ra4</MedlinePgn></Pagination><ELocationID EIdType="doi" ValidYN="Y">10.1126/scitranslmed.3000130</ELocationID><Abstract><AbstractText>In Parkinson's disease, degeneration of specific neurons in the midbrain can cause severe motor deficits, including tremors and the inability to initiate movement. The standard treatment is administration of pharmacological agents that transiently increase concentrations of brain dopamine and thereby discontinuously modulate neuronal activity in the striatum, the primary target of dopaminergic neurons. The resulting intermittent dopamine alleviates parkinsonian symptoms but is also thought to cause abnormal involuntary movements, called dyskinesias. To investigate gene therapy for Parkinson's disease, we simulated the disease in macaque monkeys by treating them with the complex I mitochondrial inhibitor 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine, which induces selective degeneration of dopamine-producing neurons. In this model, we demonstrated that injection of a tricistronic lentiviral vector encoding the critical genes for dopamine synthesis (tyrosine hydroxylase, aromatic L-amino acid decarboxylase, and guanosine 5'-triphosphate cyclohydrolase 1) into the striatum safely restored extracellular concentrations of dopamine and corrected the motor deficits for 12 months without associated dyskinesias. Gene therapy-mediated dopamine replacement may be able to correct Parkinsonism in patients without the complications of dyskinesias.</AbstractText></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Jarraya</LastName><ForeName>Béchir</ForeName><Initials>B</Initials><AffiliationInfo><Affiliation>Molecular Imaging Research Center (MIRCen), F-92265 Fontenay-aux-Roses, France. bechir.jarraya@cea.fr</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Boulet</LastName><ForeName>Sabrina</ForeName><Initials>S</Initials></Author><Author ValidYN="Y"><LastName>Ralph</LastName><ForeName>G Scott</ForeName><Initials>GS</Initials></Author><Author ValidYN="Y"><LastName>Jan</LastName><ForeName>Caroline</ForeName><Initials>C</Initials></Author><Author ValidYN="Y"><LastName>Bonvento</LastName><ForeName>Gilles</ForeName><Initials>G</Initials></Author><Author ValidYN="Y"><LastName>Azzouz</LastName><ForeName>Mimoun</ForeName><Initials>M</Initials></Author><Author ValidYN="Y"><LastName>Miskin</LastName><ForeName>James E</ForeName><Initials>JE</Initials></Author><Author ValidYN="Y"><LastName>Shin</LastName><ForeName>Masahiro</ForeName><Initials>M</Initials></Author><Author ValidYN="Y"><LastName>Delzescaux</LastName><ForeName>Thierry</ForeName><Initials>T</Initials></Author><Author ValidYN="Y"><LastName>Drouot</LastName><ForeName>Xavier</ForeName><Initials>X</Initials></Author><Author ValidYN="Y"><LastName>Hérard</LastName><ForeName>Anne-Sophie</ForeName><Initials>AS</Initials></Author><Author ValidYN="Y"><LastName>Day</LastName><ForeName>Denise M</ForeName><Initials>DM</Initials></Author><Author ValidYN="Y"><LastName>Brouillet</LastName><ForeName>Emmanuel</ForeName><Initials>E</Initials></Author><Author ValidYN="Y"><LastName>Kingsman</LastName><ForeName>Susan M</ForeName><Initials>SM</Initials></Author><Author ValidYN="Y"><LastName>Hantraye</LastName><ForeName>Philippe</ForeName><Initials>P</Initials></Author><Author ValidYN="Y"><LastName>Mitrophanous</LastName><ForeName>Kyriacos A</ForeName><Initials>KA</Initials></Author><Author ValidYN="Y"><LastName>Mazarakis</LastName><ForeName>Nicholas D</ForeName><Initials>ND</Initials></Author><Author ValidYN="Y"><LastName>Palfi</LastName><ForeName>Stéphane</ForeName><Initials>S</Initials></Author></AuthorList><Language>eng</Language><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType></PublicationTypeList></Article><MedlineJournalInfo><Country>United States</Country><MedlineTA>Sci Transl Med</MedlineTA><NlmUniqueID>101505086</NlmUniqueID><ISSNLinking>1946-6234</ISSNLinking></MedlineJournalInfo><ChemicalList><Chemical><RegistryNumber>VTD58H1Z2X</RegistryNumber><NameOfSubstance UI="D004298">Dopamine</NameOfSubstance></Chemical></ChemicalList><CitationSubset>IM</CitationSubset><MeshHeadingList><MeshHeading><DescriptorName UI="D000818" MajorTopicYN="N">Animals</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D004195" MajorTopicYN="Y">Disease Models, Animal</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D004298" MajorTopicYN="N">Dopamine</DescriptorName><QualifierName UI="Q000172" MajorTopicYN="N">deficiency</QualifierName><QualifierName UI="Q000235" MajorTopicYN="Y">genetics</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D020820" MajorTopicYN="N">Dyskinesias</DescriptorName><QualifierName UI="Q000150" MajorTopicYN="N">complications</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D015316" MajorTopicYN="Y">Genetic Therapy</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D005822" MajorTopicYN="N">Genetic Vectors</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D016086" MajorTopicYN="N">Lentivirus</DescriptorName><QualifierName UI="Q000235" MajorTopicYN="N">genetics</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D008253" MajorTopicYN="N">Macaca mulatta</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D009043" MajorTopicYN="N">Motor Activity</DescriptorName><QualifierName UI="Q000235" MajorTopicYN="N">genetics</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D010300" MajorTopicYN="N">Parkinson Disease</DescriptorName><QualifierName UI="Q000150" MajorTopicYN="N">complications</QualifierName><QualifierName UI="Q000628" MajorTopicYN="Y">therapy</QualifierName></MeshHeading></MeshHeadingList></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="entrez"><Year>2010</Year><Month>4</Month><Day>7</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="pubmed"><Year>2010</Year><Month>4</Month><Day>7</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="medline"><Year>2010</Year><Month>7</Month><Day>14</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate></History><PublicationStatus>ppublish</PublicationStatus><ArticleIdList><ArticleId IdType="pubmed">20368163</ArticleId><ArticleId IdType="pii">1/2/2ra4</ArticleId><ArticleId IdType="doi">10.1126/scitranslmed.3000130</ArticleId></ArticleIdList></PubmedData></pubmed><affiliations><list><country><li>France</li></country><region><li>Île-de-France</li></region><settlement><li>Fontenay-aux-Roses</li></settlement></list><tree><noCountry><name sortKey="Azzouz, Mimoun" sort="Azzouz, Mimoun" uniqKey="Azzouz M" first="Mimoun" last="Azzouz">Mimoun Azzouz</name><name sortKey="Bonvento, Gilles" sort="Bonvento, Gilles" uniqKey="Bonvento G" first="Gilles" last="Bonvento">Gilles Bonvento</name><name sortKey="Boulet, Sabrina" sort="Boulet, Sabrina" uniqKey="Boulet S" first="Sabrina" last="Boulet">Sabrina Boulet</name><name sortKey="Brouillet, Emmanuel" sort="Brouillet, Emmanuel" uniqKey="Brouillet E" first="Emmanuel" last="Brouillet">Emmanuel Brouillet</name><name sortKey="Day, Denise M" sort="Day, Denise M" uniqKey="Day D" first="Denise M" last="Day">Denise M. Day</name><name sortKey="Delzescaux, Thierry" sort="Delzescaux, Thierry" uniqKey="Delzescaux T" first="Thierry" last="Delzescaux">Thierry Delzescaux</name><name sortKey="Drouot, Xavier" sort="Drouot, Xavier" uniqKey="Drouot X" first="Xavier" last="Drouot">Xavier Drouot</name><name sortKey="Hantraye, Philippe" sort="Hantraye, Philippe" uniqKey="Hantraye P" first="Philippe" last="Hantraye">Philippe Hantraye</name><name sortKey="Herard, Anne Sophie" sort="Herard, Anne Sophie" uniqKey="Herard A" first="Anne-Sophie" last="Hérard">Anne-Sophie Hérard</name><name sortKey="Jan, Caroline" sort="Jan, Caroline" uniqKey="Jan C" first="Caroline" last="Jan">Caroline Jan</name><name sortKey="Kingsman, Susan M" sort="Kingsman, Susan M" uniqKey="Kingsman S" first="Susan M" last="Kingsman">Susan M. Kingsman</name><name sortKey="Mazarakis, Nicholas D" sort="Mazarakis, Nicholas D" uniqKey="Mazarakis N" first="Nicholas D" last="Mazarakis">Nicholas D. Mazarakis</name><name sortKey="Miskin, James E" sort="Miskin, James E" uniqKey="Miskin J" first="James E" last="Miskin">James E. Miskin</name><name sortKey="Mitrophanous, Kyriacos A" sort="Mitrophanous, Kyriacos A" uniqKey="Mitrophanous K" first="Kyriacos A" last="Mitrophanous">Kyriacos A. Mitrophanous</name><name sortKey="Palfi, Stephane" sort="Palfi, Stephane" uniqKey="Palfi S" first="Stéphane" last="Palfi">Stéphane Palfi</name><name sortKey="Ralph, G Scott" sort="Ralph, G Scott" uniqKey="Ralph G" first="G Scott" last="Ralph">G Scott Ralph</name><name sortKey="Shin, Masahiro" sort="Shin, Masahiro" uniqKey="Shin M" first="Masahiro" last="Shin">Masahiro Shin</name></noCountry><country name="France"><region name="Île-de-France"><name sortKey="Jarraya, Bechir" sort="Jarraya, Bechir" uniqKey="Jarraya B" first="Béchir" last="Jarraya">Béchir Jarraya</name></region></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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