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Striatal Blood–Brain Barrier Opening in Parkinson’s Disease Dementia: A Pilot Exploratory Study
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Title: | Striatal Blood–Brain Barrier Opening in Parkinson’s Disease Dementia: A Pilot Exploratory Study |
Authors : | Pineda-Pardo, José A. Gasca Salas, Carmen Fernández-Rodríguez, Beatriz Rodríguez Rojas, Rafael Álamo, Marta del Obeso Martín, Ignacio Hernández-Fernández, Frida Trompeta, Clara Martínez-Fernández, Raúl Matarazzo, Michele Mata-Marín, David Guida, Pasqualina Duque, Alicia Albillo, David Plaza de las Heras, Isabel Montero Roblas, Juan Ignacio Foffani, Guglielmo Toltsis, Gabriella Rachmilevitch, Itay Blesa, Javier Obeso Inchausti, José Ángel |
Keywords: | Parkinson's disease; Focused ultrasound; Transient blood-brain barrier; Striatal neurons |
Publisher: | Wiley |
Citation: | Pineda-Pardo JA, Gasca-Salas C, Fernández-Rodríguez B, Rodríguez-Rojas R, Del Álamo M, Obeso I, Hernández-Fernández F, Trompeta C, Martínez-Fernández R, Matarazzo M, Mata-Marín D, Guida P, Duque A, Albillo D, Plaza de Las Heras I, Montero JI, Foffani G, Toltsis G, Rachmilevitch I, Blesa J, Obeso JA. Striatal Blood-Brain Barrier Opening in Parkinson's Disease Dementia: A Pilot Exploratory Study. Mov Disord. 2022 Oct;37(10):2057-2065. doi: 10.1002/mds.29134. |
Abstract: | Background: Parkinson's disease (PD) exhibits a high prevalence of dementia as disease severity and duration progress. Focused ultrasound (FUS) has been applied for transient blood-brain barrier (BBB) opening of cortical regions in neurodegenerative disorders. The striatum is a primary target for delivery of putative therapeutic agents in PD. Objective: Here, we report a prospective, single-arm, nonrandomized, proof-of-concept, phase I clinical trial (NCT03608553 amended) in PD with dementia to test the safety and feasibility of striatal BBB opening in PD patients. Methods: Seven PD patients with cognitive impairment were treated for BBB opening in the posterior putamen. This was performed in two sessions separated by 2 to 4 weeks, where the second session included bilateral putamina opening in 3 patients. Primary outcome measures included safety and feasibility of focal striatal BBB opening. Changes in motor and cognitive functions, magnetic resonance imaging (MRI), 18 F-fluorodopa (FDOPA), and β-amyloid PET (positron emission tomography) images were determined. Results: The procedure was feasible and well tolerated, with no serious adverse events. No neurologically relevant change in motor and cognitive (battery of neuropsychological tests) functions was recognized at follow-up. MRI revealed putamen BBB closing shortly after treatment (24 hours to 14 days) and ruled out hemorrhagic and ischemic lesions. There was a discrete but significant reduction in β-amyloid uptake in the targeted region and no change in FDOPA PET. Conclusions: These initial results indicate that FUS-mediated striatal BBB opening is feasible and safe and therefore could become an effective tool to facilitate the delivery of putative neurorestorative molecules in PD. © 2022 International Parkinson and Movement Disorder Society. |
URI: | http://hdl.handle.net/10637/15350 |
Rights : | http://creativecommons.org/licenses/by-nc-nd/4.0/deed.es |
ISSN: | 0885-3185 |
Issue Date: | 28-Jun-2022 |
Center : | Universidad San Pablo-CEU |
Appears in Collections: | Medicina |
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