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タイトル: | BBB opening with focused ultrasound in nonhuman primates and Parkinson’s disease patients: Targeted AAV vector delivery and PET imaging |
著者: | 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. |
著者名の別形: | 井上, 謙一 高田, 昌彦 |
発行日: | Apr-2023 |
出版者: | American Association for the Advancement of Science (AAAS) |
誌名: | Science Advances |
巻: | 9 |
号: | 16 |
論文番号: | eadf4888 |
抄録: | 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. |
記述: | 血液脳関門開放術による遺伝子治療法の開発 --身体を傷つけない脳疾患の治療を目指して--. 京都大学プレスリリース. 2023-04-20. |
著作権等: | 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). This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial license, which permits use, distribution, and reproduction in any medium, so long as the resultant use is not for commercial advantage and provided the original work is properly cited. |
URI: | http://hdl.handle.net/2433/281763 |
DOI(出版社版): | 10.1126/sciadv.adf4888 |
PubMed ID: | 37075119 |
関連リンク: | https://www.kyoto-u.ac.jp/ja/research-news/2023-04-20 |
出現コレクション: | 学術雑誌掲載論文等 |
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