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19 results on '"Trigo‐Damas, Inés"'

7. BBB opening with focused ultrasound in nonhuman primates and Parkinson’s disease patients: Targeted AAV vector delivery and PET imaging

Author

Blesa, Javier, primary, Pineda-Pardo, José A., additional, Inoue, Ken-ichi, additional, Gasca-Salas, Carmen, additional, Balzano, Tiziano, additional, Del Rey, Natalia López-González, additional, Reinares-Sebastián, Alejandro, additional, Esteban-García, Noelia, additional, Rodríguez-Rojas, Rafael, additional, Márquez, Raquel, additional, Ciorraga, María, additional, del Álamo, Marta, additional, García-Cañamaque, Lina, additional, Ruiz de Aguiar, Santiago, additional, Rachmilevitch, Itay, additional, Trigo-Damas, Inés, additional, Takada, Masahiko, additional, and Obeso, José A., additional

Published
2023
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8. BBB opening with focused ultrasound in nonhuman primates and Parkinson’s disease patients: Targeted AAV vector delivery and PET imaging

Author

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., 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, and Obeso, José A.

Abstract

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.

Published
2023

10. Cover Image, Volume 48, Issue 5

Author

del Rey, Natalia López‐González, primary, Trigo‐Damas, Inés, additional, Obeso, José A., additional, Cavada, Carmen, additional, and Blesa, Javier, additional

Published
2022
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11. Cerebral metabolic pattern associated with progressive parkinsonism in non-human primates reveals early cortical hypometabolism

Author

Molinet-Dronda, Francisco, primary, Blesa, Javier, additional, del Rey, Natalia López-González, additional, Juri, Carlos, additional, Collantes, María, additional, Pineda-Pardo, Jose A, additional, Trigo-Damas, Inés, additional, Iglesias, Elena, additional, Hernández, Ledia F., additional, Rodríguez-Rojas, Rafael, additional, Gago, Belén, additional, Ecay, Margarita, additional, Prieto, Elena, additional, García-Cabezas, Miguel Á., additional, Cavada, Carmen, additional, Rodríguez-Oroz, María C., additional, Peñuelas, Iván, additional, and Obeso, José A., additional

Published
2022
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16. Advances in Parkinson’s Disease: 200 Years Later

Author

Del Rey, Natalia López-González, primary, Quiroga-Varela, Ana, additional, Garbayo, Elisa, additional, Carballo-Carbajal, Iria, additional, Fernández-Santiago, Rubén, additional, Monje, Mariana H. G., additional, Trigo-Damas, Inés, additional, Blanco-Prieto, María J., additional, and Blesa, Javier, additional

Published
2018
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19. Temporal dynamics of neurovascular unit changes following blood-brain barrier opening in the putamen of non-human primates.

Author

Balzano T, Pineda-Pardo JA, Esteban-García N, López-Aguirre M, Reinares-Sebastián A, Trigo-Damas I, Takada M, Obeso JA, and Blesa J

Abstract

Low-intensity focused ultrasound (LIFU) combined with intravenously circulating microbubbles has recently emerged as a novel approach for increasing delivery through the blood-brain barrier (BBB). This technique safely and transiently enables therapeutic agents to overcome the BBB, which typically poses a significant obstacle for treatment of brain disorders. However, the full impact of LIFU on the entire neurovascular unit (NVU), as well as the mechanisms and factors involved in restoring BBB integrity still require further elucidation. We conducted immunohistochemical analyses of the putamen in non-human primates to monitor changes over time [immediately post-treatment (3 h) and at 7- and 30-days post-BBB opening] in vascular, glial, and immune cells. Additionally, we examined the dynamic interactions among these elements and their role in the restorative process at the BBB level. A mild inflammatory response primarily involving microglia, astrocytes, and T- and B-lymphocytes was observed in the treated putamen acutely after BBB opening. These cells, recruited in response to the vascular changes, stimulate upregulation of PDGFRβ, a pericyte-specific marker, and VEGF-A, a pro-angiogenic factor. This was associated with vascular sprouting by 7 days post-BBB opening. Importantly, no notable long-term alterations were observed in the NVU 30 days post-BBB opening. These results offer further evidence regarding the efficacy and safety of LIFU in achieving BBB opening in the primate brain, indicating that nearly all changes in the NVU revert to baseline within 30 days post-treatment. This also suggests that angiogenesis may play an important role in restoring vascular integrity after BBB opening., Competing Interests: Declaration of competing interest J.A.O. has been a member of the Advisory Board of Insightec Ltd. (2021−2022). The authors declare that they have no other competing interests., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Published
2024
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