Blood-brain barrier opening with focused ultrasound in Parkinson's disease dementia

被引：205

作者：

Gasca-Salas, Carmen ^{[1
,2
]}

Fernandez-Rodriguez, Beatriz ^{[1
]}

Pineda-Pardo, Jose A. ^{[1
,2
]}

Rodriguez-Rojas, Rafael ^{[1
,2
]}

Obeso, Ignacio ^{[1
,2
]}

Hernandez-Fernandez, Frida ^{[1
,3
]}

del Alamo, Marta ^{[1
,2
]}

Mata, David ^{[1
,2
]}

Guida, Pasqualina ^{[1
,2
]}

Ordas-Bandera, Carlos ^{[4
]}

Ignacio Montero-Roblas, J. ^{[5
]}

Martinez-Fernandez, Raul ^{[1
,2
]}

Foffani, Guglielmo ^{[1
,2
,6
]}

Rachmilevitch, Itay ^{[7
]}

Obeso, Jose A. ^{[1
,2
]}

机构：

[1] CEU San Pablo Univ, Univ Hosp HM Puerta Sur, Fdn HM Hosp Madrid, HM CINAC, Madrid, Spain

[2] Inst Carlos III, Network Ctr Biomed Res Neurodegenerat Dis CIBERNE, Madrid, Spain

[3] Univ Europea Madrid, Fac Biomed & Hlth Sci, Dept Nursing, Madrid, Spain

[4] Hosp Univ Rey Juan Carlos, Madrid, Spain

[5] Univ Hosp HM Puerta Sur, Intens Care Unit, Madrid, Spain

[6] Hosp Nacl Paraplej, Toledo, Spain

[7] Insightec LTD, Haifa, Israel

来源：

NATURE COMMUNICATIONS | 2021年 / 12卷 / 01期

关键词：

D O I：

10.1038/s41467-021-21022-9

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

MR-guided focused ultrasound (MRgFUS), in combination with intravenous microbubble administration, has been applied for focal temporary BBB opening in patients with neurodegenerative disorders and brain tumors. MRgFUS could become a therapeutic tool for drug delivery of putative neurorestorative therapies. Treatment for Parkinson's disease with dementia (PDD) is an important unmet need. We initiated a prospective, single-arm, non-randomized, proof-of-concept, safety and feasibility phase I clinical trial (NCT03608553), which is still in progress. The primary outcomes of the study were to demonstrate the safety, feasibility and reversibility of BBB disruption in PDD, targeting the right parieto-occipito-temporal cortex where cortical pathology is foremost in this clinical state. Changes in beta -amyloid burden, brain metabolism after treatments and neuropsychological assessments, were analyzed as exploratory measurements. Five patients were recruited from October 2018 until May 2019, and received two treatment sessions separated by 2-3 weeks. The results are set out in a descriptive manner. Overall, this procedure was feasible and reversible with no serious clinical or radiological side effects. We report BBB opening in the parieto-occipito-temporal junction in 8/10 treatments in 5 patients as demonstrated by gadolinium enhancement. In all cases the procedures were uneventful and no side effects were encountered associated with BBB opening. From pre- to post-treatment, mild cognitive improvement was observed, and no major changes were detected in amyloid or fluorodeoxyglucose PET. MRgFUS-BBB opening in PDD is thus safe, reversible, and can be performed repeatedly. This study provides encouragement for the concept of BBB opening for drug delivery to treat dementia in PD and other neurodegenerative disorders. Blood brain barrier (BBB) opening is being investigated as a therapeutic approach for neurodegenerative diseases. Here, the authors report the results of a phase I trial to evaluate the feasibility and safety of BBB opening of the right parieto-occipito-temporal cortex in Parkinson ' s disease with dementia.

引用

页数：7

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