Modulation of Abnormal Metabolic Brain Networks by Experimental Therapies in a Nonhuman Primate Model of Parkinson Disease: An Application to Human Retinal Pigment Epithelial Cell Implantation.
Identifieur interne : 000143 ( PubMed/Curation ); précédent : 000142; suivant : 000144Modulation of Abnormal Metabolic Brain Networks by Experimental Therapies in a Nonhuman Primate Model of Parkinson Disease: An Application to Human Retinal Pigment Epithelial Cell Implantation.
Auteurs : Shichun Peng [États-Unis] ; Yilong Ma [États-Unis] ; Joseph Flores [Canada] ; Michael Cornfeldt ; Branka Mitrovic [États-Unis] ; David Eidelberg [États-Unis] ; Doris J. Doudet [Canada]Source :
- Journal of nuclear medicine : official publication, Society of Nuclear Medicine [ 1535-5667 ] ; 2016.
Abstract
Abnormal covariance pattern of regional metabolism associated with Parkinson disease (PD) is modulated by dopaminergic pharmacotherapy. Using high-resolution (18)F-FDG PET and network analysis, we previously derived and validated a parkinsonism-related metabolic pattern (PRP) in nonhuman primate models of PD. It is currently not known whether this network is modulated by experimental therapeutics. In this study, we examined changes in network activity by striatal implantation of human levodopa-producing retinal pigment epithelial (hRPE) cells in parkinsonian macaques and evaluated the reproducibility of network activity in a small test-retest study.
DOI: 10.2967/jnumed.115.161513
PubMed: 27056614
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Michael Cornfeldt<affiliation><nlm:affiliation>Titan Pharmaceuticals Inc., Somerville, New Jersey; and.</nlm:affiliation><wicri:noCountry code="subField">New Jersey; and</wicri:noCountry></affiliation>Le document en format XML
<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Modulation of Abnormal Metabolic Brain Networks by Experimental Therapies in a Nonhuman Primate Model of Parkinson Disease: An Application to Human Retinal Pigment Epithelial Cell Implantation.</title><author><name sortKey="Peng, Shichun" sort="Peng, Shichun" uniqKey="Peng S" first="Shichun" last="Peng">Shichun Peng</name><affiliation wicri:level="2"><nlm:affiliation>Center for Neurosciences, The Feinstein Institute for Medical Research, Manhasset, New York, New York.</nlm:affiliation><country xml:lang="fr">États-Unis</country><placeName><region type="state">État de New York</region></placeName><wicri:cityArea>Center for Neurosciences, The Feinstein Institute for Medical Research, Manhasset, New York</wicri:cityArea></affiliation></author><author><name sortKey="Ma, Yilong" sort="Ma, Yilong" uniqKey="Ma Y" first="Yilong" last="Ma">Yilong Ma</name><affiliation wicri:level="1"><nlm:affiliation>Center for Neurosciences, The Feinstein Institute for Medical Research, Manhasset, New York, New York yma@nshs.edu.</nlm:affiliation><country wicri:rule="url">États-Unis</country><wicri:regionArea>Center for Neurosciences, The Feinstein Institute for Medical Research, Manhasset, New York</wicri:regionArea></affiliation></author><author><name sortKey="Flores, Joseph" sort="Flores, Joseph" uniqKey="Flores J" first="Joseph" last="Flores">Joseph Flores</name><affiliation wicri:level="1"><nlm:affiliation>Department of Neurology, University of British Columbia, Vancouver, British Columbia, Canada.</nlm:affiliation><country xml:lang="fr">Canada</country><wicri:regionArea>Department of Neurology, University of British Columbia, Vancouver, British Columbia</wicri:regionArea></affiliation></author><author><name sortKey="Cornfeldt, Michael" sort="Cornfeldt, Michael" uniqKey="Cornfeldt M" first="Michael" last="Cornfeldt">Michael Cornfeldt</name><affiliation><nlm:affiliation>Titan Pharmaceuticals Inc., Somerville, New Jersey; and.</nlm:affiliation><wicri:noCountry code="subField">New Jersey; and</wicri:noCountry></affiliation></author><author><name sortKey="Mitrovic, Branka" sort="Mitrovic, Branka" uniqKey="Mitrovic B" first="Branka" last="Mitrovic">Branka Mitrovic</name><affiliation wicri:level="2"><nlm:affiliation>Bayer HealthCare Pharmaceuticals Inc., Richmond, California.</nlm:affiliation><country>États-Unis</country><placeName><region type="state">Californie</region></placeName><wicri:cityArea>Bayer HealthCare Pharmaceuticals Inc., Richmond</wicri:cityArea></affiliation></author><author><name sortKey="Eidelberg, David" sort="Eidelberg, David" uniqKey="Eidelberg D" first="David" last="Eidelberg">David Eidelberg</name><affiliation wicri:level="2"><nlm:affiliation>Center for Neurosciences, The Feinstein Institute for Medical Research, Manhasset, New York, New York.</nlm:affiliation><country xml:lang="fr">États-Unis</country><placeName><region type="state">État de New York</region></placeName><wicri:cityArea>Center for Neurosciences, The Feinstein Institute for Medical Research, Manhasset, New York</wicri:cityArea></affiliation></author><author><name sortKey="Doudet, Doris J" sort="Doudet, Doris J" uniqKey="Doudet D" first="Doris J" last="Doudet">Doris J. Doudet</name><affiliation wicri:level="1"><nlm:affiliation>Department of Neurology, University of British Columbia, Vancouver, British Columbia, Canada.</nlm:affiliation><country xml:lang="fr">Canada</country><wicri:regionArea>Department of Neurology, University of British Columbia, Vancouver, British Columbia</wicri:regionArea></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PubMed</idno><date when="2016">2016</date><idno type="RBID">pubmed:27056614</idno><idno type="pmid">27056614</idno><idno type="doi">10.2967/jnumed.115.161513</idno><idno type="wicri:Area/PubMed/Corpus">000143</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Corpus" wicri:corpus="PubMed">000143</idno><idno type="wicri:Area/PubMed/Curation">000143</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Curation">000143</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en">Modulation of Abnormal Metabolic Brain Networks by Experimental Therapies in a Nonhuman Primate Model of Parkinson Disease: An Application to Human Retinal Pigment Epithelial Cell Implantation.</title><author><name sortKey="Peng, Shichun" sort="Peng, Shichun" uniqKey="Peng S" first="Shichun" last="Peng">Shichun Peng</name><affiliation wicri:level="2"><nlm:affiliation>Center for Neurosciences, The Feinstein Institute for Medical Research, Manhasset, New York, New York.</nlm:affiliation><country xml:lang="fr">États-Unis</country><placeName><region type="state">État de New York</region></placeName><wicri:cityArea>Center for Neurosciences, The Feinstein Institute for Medical Research, Manhasset, New York</wicri:cityArea></affiliation></author><author><name sortKey="Ma, Yilong" sort="Ma, Yilong" uniqKey="Ma Y" first="Yilong" last="Ma">Yilong Ma</name><affiliation wicri:level="1"><nlm:affiliation>Center for Neurosciences, The Feinstein Institute for Medical Research, Manhasset, New York, New York yma@nshs.edu.</nlm:affiliation><country wicri:rule="url">États-Unis</country><wicri:regionArea>Center for Neurosciences, The Feinstein Institute for Medical Research, Manhasset, New York</wicri:regionArea></affiliation></author><author><name sortKey="Flores, Joseph" sort="Flores, Joseph" uniqKey="Flores J" first="Joseph" last="Flores">Joseph Flores</name><affiliation wicri:level="1"><nlm:affiliation>Department of Neurology, University of British Columbia, Vancouver, British Columbia, Canada.</nlm:affiliation><country xml:lang="fr">Canada</country><wicri:regionArea>Department of Neurology, University of British Columbia, Vancouver, British Columbia</wicri:regionArea></affiliation></author><author><name sortKey="Cornfeldt, Michael" sort="Cornfeldt, Michael" uniqKey="Cornfeldt M" first="Michael" last="Cornfeldt">Michael Cornfeldt</name><affiliation><nlm:affiliation>Titan Pharmaceuticals Inc., Somerville, New Jersey; and.</nlm:affiliation><wicri:noCountry code="subField">New Jersey; and</wicri:noCountry></affiliation></author><author><name sortKey="Mitrovic, Branka" sort="Mitrovic, Branka" uniqKey="Mitrovic B" first="Branka" last="Mitrovic">Branka Mitrovic</name><affiliation wicri:level="2"><nlm:affiliation>Bayer HealthCare Pharmaceuticals Inc., Richmond, California.</nlm:affiliation><country>États-Unis</country><placeName><region type="state">Californie</region></placeName><wicri:cityArea>Bayer HealthCare Pharmaceuticals Inc., Richmond</wicri:cityArea></affiliation></author><author><name sortKey="Eidelberg, David" sort="Eidelberg, David" uniqKey="Eidelberg D" first="David" last="Eidelberg">David Eidelberg</name><affiliation wicri:level="2"><nlm:affiliation>Center for Neurosciences, The Feinstein Institute for Medical Research, Manhasset, New York, New York.</nlm:affiliation><country xml:lang="fr">États-Unis</country><placeName><region type="state">État de New York</region></placeName><wicri:cityArea>Center for Neurosciences, The Feinstein Institute for Medical Research, Manhasset, New York</wicri:cityArea></affiliation></author><author><name sortKey="Doudet, Doris J" sort="Doudet, Doris J" uniqKey="Doudet D" first="Doris J" last="Doudet">Doris J. Doudet</name><affiliation wicri:level="1"><nlm:affiliation>Department of Neurology, University of British Columbia, Vancouver, British Columbia, Canada.</nlm:affiliation><country xml:lang="fr">Canada</country><wicri:regionArea>Department of Neurology, University of British Columbia, Vancouver, British Columbia</wicri:regionArea></affiliation></author></analytic><series><title level="j">Journal of nuclear medicine : official publication, Society of Nuclear Medicine</title><idno type="eISSN">1535-5667</idno><imprint><date when="2016" type="published">2016</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Abnormal covariance pattern of regional metabolism associated with Parkinson disease (PD) is modulated by dopaminergic pharmacotherapy. Using high-resolution (18)F-FDG PET and network analysis, we previously derived and validated a parkinsonism-related metabolic pattern (PRP) in nonhuman primate models of PD. It is currently not known whether this network is modulated by experimental therapeutics. In this study, we examined changes in network activity by striatal implantation of human levodopa-producing retinal pigment epithelial (hRPE) cells in parkinsonian macaques and evaluated the reproducibility of network activity in a small test-retest study.</div></front></TEI><pubmed><MedlineCitation Status="In-Process" Owner="NLM"><PMID Version="1">27056614</PMID><DateCreated><Year>2016</Year><Month>04</Month><Day>08</Day></DateCreated><DateRevised><Year>2017</Year><Month>04</Month><Day>03</Day></DateRevised><Article PubModel="Print-Electronic"><Journal><ISSN IssnType="Electronic">1535-5667</ISSN><JournalIssue CitedMedium="Internet"><Volume>57</Volume><Issue>10</Issue><PubDate><Year>2016</Year><Month>Oct</Month></PubDate></JournalIssue><Title>Journal of nuclear medicine : official publication, Society of Nuclear Medicine</Title><ISOAbbreviation>J. Nucl. Med.</ISOAbbreviation></Journal><ArticleTitle>Modulation of Abnormal Metabolic Brain Networks by Experimental Therapies in a Nonhuman Primate Model of Parkinson Disease: An Application to Human Retinal Pigment Epithelial Cell Implantation.</ArticleTitle><Pagination><MedlinePgn>1591-1598</MedlinePgn></Pagination><Abstract><AbstractText>Abnormal covariance pattern of regional metabolism associated with Parkinson disease (PD) is modulated by dopaminergic pharmacotherapy. Using high-resolution (18)F-FDG PET and network analysis, we previously derived and validated a parkinsonism-related metabolic pattern (PRP) in nonhuman primate models of PD. It is currently not known whether this network is modulated by experimental therapeutics. In this study, we examined changes in network activity by striatal implantation of human levodopa-producing retinal pigment epithelial (hRPE) cells in parkinsonian macaques and evaluated the reproducibility of network activity in a small test-retest study.</AbstractText><AbstractText Label="METHODS" NlmCategory="METHODS">(18)F-FDG PET scans were acquired in 8 healthy macaques and 8 macaques with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced bilateral nigrostriatal dopaminergic lesions after unilateral putaminal implantation of hRPE cells or sham surgery. PRP activity was measured prospectively in all animals and in a subset of test-retest animals using a network quantification approach. Network activity and regional metabolic values were compared on a hemispheric basis between animal groups and treatment conditions.</AbstractText><AbstractText Label="RESULTS" NlmCategory="RESULTS">All individual macaques showed clinical improvement after hRPE cell implantation compared with the sham surgery. PRP activity was elevated in the untreated MPTP hemispheres relative to those of the normal controls (P < 0.00005) but was reduced (P < 0.05) in the hRPE-implanted hemispheres. The modulation observed in network activity was supported by concurrent local and remote changes in regional glucose metabolism. PRP activity remained unchanged in the untreated MPTP hemispheres versus the sham-operated hemispheres. PRP activity was also stable (P ≥ 0.29) and correlated (R(2) ≥ 0.926; P < 0.00005) in the test-retest hemispheres. These findings were highly reproducible across several PRP topographies generated in multiple cohorts of parkinsonian and healthy macaques.</AbstractText><AbstractText Label="CONCLUSION" NlmCategory="CONCLUSIONS">We have demonstrated long-term therapeutic effects of hRPE cell implantation in nonhuman primate models of PD. The implantation of such levodopa-producing cells can concurrently decrease the elevated metabolic network activity in parkinsonian brains on an individual basis. These results parallel the analogous findings reported in patients with PD undergoing levodopa therapy and other symptomatic interventions. With further validation in large samples, (18)F-FDG PET imaging with network analysis may provide a viable biomarker for assessing treatment response in animal models of PD after experimental therapies.</AbstractText><CopyrightInformation>© 2016 by the Society of Nuclear Medicine and Molecular Imaging, Inc.</CopyrightInformation></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Peng</LastName><ForeName>Shichun</ForeName><Initials>S</Initials><AffiliationInfo><Affiliation>Center for Neurosciences, The Feinstein Institute for Medical Research, Manhasset, New York, New York.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Ma</LastName><ForeName>Yilong</ForeName><Initials>Y</Initials><AffiliationInfo><Affiliation>Center for Neurosciences, The Feinstein Institute for Medical Research, Manhasset, New York, New York yma@nshs.edu.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Flores</LastName><ForeName>Joseph</ForeName><Initials>J</Initials><AffiliationInfo><Affiliation>Department of Neurology, University of British Columbia, Vancouver, British Columbia, Canada.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Cornfeldt</LastName><ForeName>Michael</ForeName><Initials>M</Initials><AffiliationInfo><Affiliation>Titan Pharmaceuticals Inc., Somerville, New Jersey; and.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Mitrovic</LastName><ForeName>Branka</ForeName><Initials>B</Initials><AffiliationInfo><Affiliation>Bayer HealthCare Pharmaceuticals Inc., Richmond, California.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Eidelberg</LastName><ForeName>David</ForeName><Initials>D</Initials><AffiliationInfo><Affiliation>Center for Neurosciences, The Feinstein Institute for Medical Research, Manhasset, New York, New York.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Doudet</LastName><ForeName>Doris J</ForeName><Initials>DJ</Initials><AffiliationInfo><Affiliation>Department of Neurology, University of British Columbia, Vancouver, British Columbia, Canada.</Affiliation></AffiliationInfo></Author></AuthorList><Language>eng</Language><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType></PublicationTypeList><ArticleDate DateType="Electronic"><Year>2016</Year><Month>04</Month><Day>07</Day></ArticleDate></Article><MedlineJournalInfo><Country>United States</Country><MedlineTA>J Nucl Med</MedlineTA><NlmUniqueID>0217410</NlmUniqueID><ISSNLinking>0161-5505</ISSNLinking></MedlineJournalInfo><CommentsCorrectionsList><CommentsCorrections RefType="Cites"><RefSource>J Nucl Med. 2013 May;54(5):785-92</RefSource><PMID Version="1">23503731</PMID></CommentsCorrections><CommentsCorrections RefType="Cites"><RefSource>J Cereb Blood Flow Metab. 2012 Apr;32(4):633-42</RefSource><PMID 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Jan;34(1):35-61</RefSource><PMID Version="1">22926166</PMID></CommentsCorrections><CommentsCorrections RefType="Cites"><RefSource>Neuroimage. 2011 Jun 1;56(3):1463-8</RefSource><PMID Version="1">21396455</PMID></CommentsCorrections><CommentsCorrections RefType="Cites"><RefSource>J Nucl Med. 2011 Jan;52(1):90-7</RefSource><PMID Version="1">21149480</PMID></CommentsCorrections><CommentsCorrections RefType="Cites"><RefSource>Ann Neurol. 2012 Jul;72(1):32-40</RefSource><PMID Version="1">22829267</PMID></CommentsCorrections><CommentsCorrections RefType="Cites"><RefSource>J Cereb Blood Flow Metab. 2007 Mar;27(3):597-605</RefSource><PMID Version="1">16804550</PMID></CommentsCorrections></CommentsCorrectionsList><KeywordList Owner="NOTNLM"><Keyword MajorTopicYN="N">FDG PET</Keyword><Keyword MajorTopicYN="N">dopamine cell transplantation</Keyword><Keyword MajorTopicYN="N">network analysis</Keyword><Keyword MajorTopicYN="N">parkinsonism</Keyword><Keyword MajorTopicYN="N">primate 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