BBB opening with focused ultrasound in nonhuman primates and Parkinson's disease patients: Targeted AAV vector delivery and PET imaging.
BBB opening with focused ultrasound in nonhuman primates and Parkinson's disease patients: Targeted AAV vector delivery and PET imaging.
复制标题
DOI：
10.1126/sciadv.adf4888
复制
发表时间：
2023-04-21
期刊：
影响因子：
13.6
通讯作者：
Obeso, Jose A.
中科院分区：
文献类型：
--
作者：
Blesa, Javier;Pineda-Pardo, Jose A.;Inoue, Ken-ichi;Gasca-Salas, Carmen;Balzano, Tiziano;Lopez-Gonzalez Del Rey, Natalia;Reinares-Sebastian, Alejandro;Esteban-Garcia, Noelia;Rodriguez-Rojas, Rafael;Marquez, Raquel;Ciorraga, Maria;del Alamo, Marta;Garcia-Canamaque, Lina;Ruiz de Aguiar, Santiago;Rachmilevitch, Itay;Trigo-Damas, Ines;Takada, Masahiko;Obeso, Jose A.
在非人灵长类动物中进行脑内载体递送一直是一项重大挑战。我们报告了在成年猕猴中使用低强度聚焦超声成功打开血脑屏障，并将腺相关病毒9型载体局部递送至帕金森病相关脑区的研究结果。开口耐受性良好，通常没有相关的异常磁共振成像信号。在已确认血脑屏障打开的区域特异性地观察到神经元绿色荧光蛋白表达。在三名帕金森病患者中也安全地展示了类似的血脑屏障打开情况。在这些患者以及一只猴子中，基于正电子发射断层扫描，血脑屏障打开后在壳核和中脑区域出现了¹⁸F - 胆碱摄取。这表明原本无法进入脑实质的分子发生了局部和细胞结合。这种方法的微创性可能有助于基因治疗中局部病毒载体的递送，并可能允许对神经退行性疾病进行早期和反复干预。
通过聚焦超声打开血脑屏障将靶向腺相关病毒载体递送至灵长类动物大脑可能有助于治疗。
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. The delivery of a targeted AAV vector into a primate brain via BBB opening with focused ultrasounds could facilitate treatments.
登录
查看更多内容
影响因子：
25
作者：
Chan KY;Jang MJ;Yoo BB;Greenbaum A;Ravi N;Wu WL;Sánchez-Guardado L;Lois C;Mazmanian SK;Deverman BE;Gradinaru V
通讯作者：
Gradinaru V
影响因子：
7.2
作者：
Daneman, Richard;Prat, Alexandre
通讯作者：
Prat, Alexandre
用于针对小儿疾病的脊髓，大脑和周围组织的大物种中的全身基因递送。
DOI：
10.1038/mt.2011.157
发表时间：
2011-11
期刊：
Molecular therapy : the journal of the American Society of Gene Therapy
影响因子：
--
作者：
通讯作者：
--
影响因子：
50
作者：
Deuschl, Guenther;Beghi, Ettore;Feigin, Valery L.
通讯作者：
Feigin, Valery L.
影响因子：
9.7
作者：
Vaquero JJ;Kinahan P
通讯作者：
Kinahan P