BBB opening with focused ultrasound in nonhuman primates and Parkinson’s disease patients: Targeted AAV vector delivery and PET imaging
Year: 2023
Type: article
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 18 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.
Source: Science Advances
Authors: Javier Blesa, José A. Pineda-Pardo, Ken-ichi Inoue, Carmen Gasca-Salas, Tiziano Balzano, Natalia López-González Del Rey, Alejandro Reinares-Sebastián, Noelia Esteban-García, Rafael Rodríguez-Rojas, Raquel Márquez, María Ciorraga, Marta del Álamo, Lina García-Cañamaque, Santiago Ruiz de Aguiar, Itay Rachmilevitch, Inés Trigo-Damas, Masahiko Takada, José A. Obeso
Institutions: Biomedical Research Networking Center on Neurodegenerative Diseases, HM Hospitales, University Hospital HM Puerta del Sur, Kyoto University, Institute for the Evolutionary Origins of Human Behavior, Kyoto University, Universidad San Pablo CEU, Instituto Cajal, Universidad Autónoma de Madrid, The University of Osaka
Language: English
Subfield: Biomedical Engineering
Field: Engineering
Domain: Physical Sciences
Open Access status: gold
Estimated APC paid: $4,500
Funders: Focused Ultrasound Foundation, Fundación BBVA, Fundación de Investigación HM Hospitales, Fundación Mapfre, Ministerio de Ciencia e Innovación, Banco Bilbao Vizcaya Argentaria, Fundación Tatiana Pérez de Guzmán el Bueno, Japan Society for the Promotion of Science, Instituto de Salud Carlos III
Awards: G1560111206, Elucidating the primate basis of neurobiological mechanisms underlying developmental disorders, G3690828678, Development of a method for creating primate disease models via whole-brain gene transfer technique, マルチモーダルスキルを支える大脳皮質－大脳基底核連関の情報処理様式, G6816651011, Enfermedad de Parkinson: vulnerabilidad neuronal y progresión de la enfermedad
OpenAlex ID: W4366603281