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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Autores: Blesa, Javier, Inoue, Ken-Ichi, Gasca-Salas, Carmen, Balzano, Tiziano, 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, Pineda-Pardo, José A., Obeso, José, Lopez-Gonzalez del Rey, Natalia
Tipo de recurso: artículo
Fecha de publicación:2023
País:España
Institución:Universidad Camilo José Cela (UCJC)
Repositorio:Depósito Digital e-UCJC
OAI Identifier:oai:repositorio.ucjc.edu:20.500.12020/1525
Acceso en línea:https://www.science.org/doi/10.1126/sciadv.adf4888?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub%20%200pubmed
http://hdl.handle.net/20.500.12020/1525
https://doi.org/10.1126/sciadv.adf4888
Access Level:acceso abierto
Palabra clave:Ciencias Biomédicas
Parkinson's Disease
Gene Therapy
Focused Ultrasound
32 Ciencias Médicas
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oai_identifier_str oai:repositorio.ucjc.edu:20.500.12020/1525
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repository_id_str
spelling BBB opening with focused ultrasound in nonhuman primates and Parkinson's disease patients: Targeted AAV vector delivery and PET imagingBlesa, JavierInoue, Ken-IchiGasca-Salas, CarmenBalzano, TizianoReinares-Sebastián, AlejandroEsteban-García, NoeliaRodríguez-Rojas, RafaelMárquez, RaquelCiorraga, MaríaDel Álamo, MartaGarcía-Cañamaque, LinaRuiz de Aguiar, SantiagoRachmilevitch, ItayTrigo-Damas, InésTakada, MasahikoPineda-Pardo, José A.Obeso, JoséLopez-Gonzalez del Rey, NataliaCiencias BiomédicasParkinson's DiseaseGene TherapyFocused Ultrasound32 Ciencias MédicasIntracerebral 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 18F-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.American Association for the Advancement of Science2023info:eu-repo/semantics/articlehttps://www.science.org/doi/10.1126/sciadv.adf4888?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub%20%200pubmedhttp://hdl.handle.net/20.500.12020/1525https://doi.org/10.1126/sciadv.adf4888reponame:Depósito Digital e-UCJCinstname:Universidad Camilo José Cela (UCJC)Inglésinfo:eu-repo/semantics/openAccessoai:repositorio.ucjc.edu:20.500.12020/15252026-05-27T07:36:51Z
dc.title.none.fl_str_mv BBB opening with focused ultrasound in nonhuman primates and Parkinson's disease patients: Targeted AAV vector delivery and PET imaging
title BBB opening with focused ultrasound in nonhuman primates and Parkinson's disease patients: Targeted AAV vector delivery and PET imaging
spellingShingle BBB opening with focused ultrasound in nonhuman primates and Parkinson's disease patients: Targeted AAV vector delivery and PET imaging
Blesa, Javier
Ciencias Biomédicas
Parkinson's Disease
Gene Therapy
Focused Ultrasound
32 Ciencias Médicas
title_short BBB opening with focused ultrasound in nonhuman primates and Parkinson's disease patients: Targeted AAV vector delivery and PET imaging
title_full BBB opening with focused ultrasound in nonhuman primates and Parkinson's disease patients: Targeted AAV vector delivery and PET imaging
title_fullStr BBB opening with focused ultrasound in nonhuman primates and Parkinson's disease patients: Targeted AAV vector delivery and PET imaging
title_full_unstemmed BBB opening with focused ultrasound in nonhuman primates and Parkinson's disease patients: Targeted AAV vector delivery and PET imaging
title_sort BBB opening with focused ultrasound in nonhuman primates and Parkinson's disease patients: Targeted AAV vector delivery and PET imaging
dc.creator.none.fl_str_mv Blesa, Javier
Inoue, Ken-Ichi
Gasca-Salas, Carmen
Balzano, Tiziano
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
Pineda-Pardo, José A.
Obeso, José
Lopez-Gonzalez del Rey, Natalia
author Blesa, Javier
author_facet Blesa, Javier
Inoue, Ken-Ichi
Gasca-Salas, Carmen
Balzano, Tiziano
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
Pineda-Pardo, José A.
Obeso, José
Lopez-Gonzalez del Rey, Natalia
author_role author
author2 Inoue, Ken-Ichi
Gasca-Salas, Carmen
Balzano, Tiziano
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
Pineda-Pardo, José A.
Obeso, José
Lopez-Gonzalez del Rey, Natalia
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Ciencias Biomédicas
Parkinson's Disease
Gene Therapy
Focused Ultrasound
32 Ciencias Médicas
topic Ciencias Biomédicas
Parkinson's Disease
Gene Therapy
Focused Ultrasound
32 Ciencias Médicas
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 18F-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.
publishDate 2023
dc.date.none.fl_str_mv 2023
dc.type.none.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv https://www.science.org/doi/10.1126/sciadv.adf4888?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub%20%200pubmed
http://hdl.handle.net/20.500.12020/1525
https://doi.org/10.1126/sciadv.adf4888
url https://www.science.org/doi/10.1126/sciadv.adf4888?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub%20%200pubmed
http://hdl.handle.net/20.500.12020/1525
https://doi.org/10.1126/sciadv.adf4888
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv American Association for the Advancement of Science
publisher.none.fl_str_mv American Association for the Advancement of Science
dc.source.none.fl_str_mv reponame:Depósito Digital e-UCJC
instname:Universidad Camilo José Cela (UCJC)
instname_str Universidad Camilo José Cela (UCJC)
reponame_str Depósito Digital e-UCJC
collection Depósito Digital e-UCJC
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,81155

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