BBB opening with focused ultrasound in nonhuman primates and Parkinson's disease patients: Targeted AAV vector delivery and PET imaging
Intracerebral vector delivery in nonhuman primates has been a major challenge. We report successful blood-brain barrier opening and focal delivery of adeno-associated virus serotype 9 vectors into brain regions involved in Parkinson's disease using low-intensity focus ultrasound in adult macaqu...
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| Veröffentlicht in: | Science advances 2023-04, Vol.9 (16), p.eadf4888-eadf4888 |
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| creator | Blesa, Javier Pineda-Pardo, José A Inoue, Ken-Ichi Gasca-Salas, Carmen Balzano, Tiziano Del Rey, Natalia López-González Reinares-Sebastián, Alejandro Esteban-García, Noelia Rodríguez-Rojas, Rafael Márquez, Raquel Ciorraga, María Del Álamo, Marta García-Cañamaque, Lina Ruiz de Aguiar, Santiago Rachmilevitch, Itay Trigo-Damas, Inés Takada, Masahiko Obeso, José A |
| description | Intracerebral vector delivery in nonhuman primates has been a major challenge. We report successful blood-brain barrier opening and focal delivery of adeno-associated virus serotype 9 vectors into brain regions involved in Parkinson's disease using low-intensity focus ultrasound in adult macaque monkeys. Openings were well tolerated with generally no associated abnormal magnetic resonance imaging signals. Neuronal green fluorescent protein expression was observed specifically in regions with confirmed blood-brain barrier opening. Similar blood-brain barrier openings were safely demonstrated in three patients with Parkinson's disease. In these patients and in one monkey, blood-brain barrier opening was followed by
F-Choline uptake in the putamen and midbrain regions based on positron emission tomography. This indicates focal and cellular binding of molecules that otherwise would not enter the brain parenchyma. The less-invasive nature of this methodology could facilitate focal viral vector delivery for gene therapy and might allow early and repeated interventions to treat neurodegenerative disorders. |
| doi_str_mv | 10.1126/sciadv.adf4888 |
| format | Article |
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F-Choline uptake in the putamen and midbrain regions based on positron emission tomography. This indicates focal and cellular binding of molecules that otherwise would not enter the brain parenchyma. The less-invasive nature of this methodology could facilitate focal viral vector delivery for gene therapy and might allow early and repeated interventions to treat neurodegenerative disorders.</description><identifier>ISSN: 2375-2548</identifier><identifier>EISSN: 2375-2548</identifier><identifier>DOI: 10.1126/sciadv.adf4888</identifier><identifier>PMID: 37075119</identifier><language>eng</language><publisher>United States: American Association for the Advancement of Science</publisher><subject>Animals ; Blood-Brain Barrier - metabolism ; Brain - metabolism ; Diseases and Disorders ; Macaca ; Magnetic Resonance Imaging ; Neuroscience ; Parkinson Disease - diagnostic imaging ; Parkinson Disease - genetics ; Parkinson Disease - therapy ; Positron-Emission Tomography ; SciAdv r-articles</subject><ispartof>Science advances, 2023-04, Vol.9 (16), p.eadf4888-eadf4888</ispartof><rights>Copyright © 2023 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC). 2023 The Authors</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c435t-4eedba8db7a149ef42f4d83d69372cda5639f492531a1e5f1706cdfa443f05713</citedby><cites>FETCH-LOGICAL-c435t-4eedba8db7a149ef42f4d83d69372cda5639f492531a1e5f1706cdfa443f05713</cites><orcidid>0000-0002-1546-1825 ; 0000-0001-7411-8106 ; 0000-0001-6523-2206 ; 0000-0003-1632-4432 ; 0000-0002-6996-8613 ; 0000-0002-8776-0031 ; 0000-0002-2903-199X ; 0000-0002-6519-4200 ; 0000-0003-0774-2333 ; 0000-0002-4257-1325 ; 0000-0001-8438-6956 ; 0000-0002-5683-5280 ; 0000-0002-7821-2973 ; 0000-0002-2741-3054 ; 0000-0003-4290-502X ; 0000-0002-4175-7611</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC10115413/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC10115413/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,27901,27902,53766,53768</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/37075119$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Blesa, Javier</creatorcontrib><creatorcontrib>Pineda-Pardo, José A</creatorcontrib><creatorcontrib>Inoue, Ken-Ichi</creatorcontrib><creatorcontrib>Gasca-Salas, Carmen</creatorcontrib><creatorcontrib>Balzano, Tiziano</creatorcontrib><creatorcontrib>Del Rey, Natalia López-González</creatorcontrib><creatorcontrib>Reinares-Sebastián, Alejandro</creatorcontrib><creatorcontrib>Esteban-García, Noelia</creatorcontrib><creatorcontrib>Rodríguez-Rojas, Rafael</creatorcontrib><creatorcontrib>Márquez, Raquel</creatorcontrib><creatorcontrib>Ciorraga, María</creatorcontrib><creatorcontrib>Del Álamo, Marta</creatorcontrib><creatorcontrib>García-Cañamaque, Lina</creatorcontrib><creatorcontrib>Ruiz de Aguiar, Santiago</creatorcontrib><creatorcontrib>Rachmilevitch, Itay</creatorcontrib><creatorcontrib>Trigo-Damas, Inés</creatorcontrib><creatorcontrib>Takada, Masahiko</creatorcontrib><creatorcontrib>Obeso, José A</creatorcontrib><title>BBB opening with focused ultrasound in nonhuman primates and Parkinson's disease patients: Targeted AAV vector delivery and PET imaging</title><title>Science advances</title><addtitle>Sci Adv</addtitle><description>Intracerebral vector delivery in nonhuman primates has been a major challenge. We report successful blood-brain barrier opening and focal delivery of adeno-associated virus serotype 9 vectors into brain regions involved in Parkinson's disease using low-intensity focus ultrasound in adult macaque monkeys. Openings were well tolerated with generally no associated abnormal magnetic resonance imaging signals. Neuronal green fluorescent protein expression was observed specifically in regions with confirmed blood-brain barrier opening. Similar blood-brain barrier openings were safely demonstrated in three patients with Parkinson's disease. In these patients and in one monkey, blood-brain barrier opening was followed by
F-Choline uptake in the putamen and midbrain regions based on positron emission tomography. This indicates focal and cellular binding of molecules that otherwise would not enter the brain parenchyma. 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F-Choline uptake in the putamen and midbrain regions based on positron emission tomography. This indicates focal and cellular binding of molecules that otherwise would not enter the brain parenchyma. The less-invasive nature of this methodology could facilitate focal viral vector delivery for gene therapy and might allow early and repeated interventions to treat neurodegenerative disorders.</abstract><cop>United States</cop><pub>American Association for the Advancement of Science</pub><pmid>37075119</pmid><doi>10.1126/sciadv.adf4888</doi><orcidid>https://orcid.org/0000-0002-1546-1825</orcidid><orcidid>https://orcid.org/0000-0001-7411-8106</orcidid><orcidid>https://orcid.org/0000-0001-6523-2206</orcidid><orcidid>https://orcid.org/0000-0003-1632-4432</orcidid><orcidid>https://orcid.org/0000-0002-6996-8613</orcidid><orcidid>https://orcid.org/0000-0002-8776-0031</orcidid><orcidid>https://orcid.org/0000-0002-2903-199X</orcidid><orcidid>https://orcid.org/0000-0002-6519-4200</orcidid><orcidid>https://orcid.org/0000-0003-0774-2333</orcidid><orcidid>https://orcid.org/0000-0002-4257-1325</orcidid><orcidid>https://orcid.org/0000-0001-8438-6956</orcidid><orcidid>https://orcid.org/0000-0002-5683-5280</orcidid><orcidid>https://orcid.org/0000-0002-7821-2973</orcidid><orcidid>https://orcid.org/0000-0002-2741-3054</orcidid><orcidid>https://orcid.org/0000-0003-4290-502X</orcidid><orcidid>https://orcid.org/0000-0002-4175-7611</orcidid><oa>free_for_read</oa></addata></record> |
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| source | MEDLINE; DOAJ Directory of Open Access Journals; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; PubMed Central |
| subjects | Animals Blood-Brain Barrier - metabolism Brain - metabolism Diseases and Disorders Macaca Magnetic Resonance Imaging Neuroscience Parkinson Disease - diagnostic imaging Parkinson Disease - genetics Parkinson Disease - therapy Positron-Emission Tomography SciAdv r-articles |
| title | BBB opening with focused ultrasound in nonhuman primates and Parkinson's disease patients: Targeted AAV vector delivery and PET imaging |
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