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. 2024 Oct 16;95(11):1089-1092.
doi: 10.1136/jnnp-2023-332967.

Nigrostriatal blood-brain barrier opening in Parkinson's disease

Carmen Gasca-Salas  1   2   3 , José A Pineda-Pardo  1   2   3 , Marta Del Álamo  1   2 , Tamara Jiménez  1   2 , Clara Trompeta  1   2   4 , Gabriella Toltsis  5 , Lina Garcia-Cañamaque  6 , Beatriz Fernández-Rodríguez  1   2 , Michele Matarazzo  1   2   3 , Isabel Plaza de Las Heras  6 , Elena Natera-Villalba  1   2 , Raúl Martínez-Fernández  1   2   3 , Alicia Duque  7 , Santiago Ruiz de Aguiar  8 , Javier Blesa  1   2   3   9 , Itay Rachmilevich  5 , José A Obeso  10   2   3
Affiliations

Nigrostriatal blood-brain barrier opening in Parkinson's disease

Carmen Gasca-Salas et al. J Neurol Neurosurg Psychiatry. .

Abstract

Background: The nigrostriatal system is especially vulnerable to neurodegeneration in Parkinson's disease (PD) and the blood-brain barrier (BBB) is a limiting factor for delivery of therapeutic agents to the brain. This pilot study aimed to demonstrate safety, feasibility and tissue penetration (by 18F-Choline-positron emission tomography (PET)) of MR-guided focused ultrasound (MRgFUS) simultaneous BBB opening (BBB-O) in the substantia nigra (SN) and putamen in PD.

Methods: Three patients underwent MRgFUS for midbrain and putamen BBB-O. Patients were evaluated clinically and underwent brain MRI with gadolinium (baseline, 24 hours, 14 days and 3 months postprocedure). In two patients, BBB-O was repeated after 2-3 weeks, and 18F-Choline-PET was performed immediately after.

Results: The right SN and putamen were simultaneously opened unilaterally in 3 patients once and the left SN in 1 patient in a different session. No severe clinical or neuroimaging adverse events developed in any patient. 18F-Choline-PET uptake was enhanced in the targeted SN and putamen regions.

Conclusion: BBB-O of the nigrostriatal system is a feasible and well-tolerated approach in patients with PD. 18F-Choline-PET uptake indicates penetration into the parenchyma after BBB-O, which suggests that the opening is functionally effective. This minimally invasive technique could facilitate delivery of putative neurorestorative molecules to brain regions vulnerable to neurodegeneration.

Keywords: BLOOD-BRAIN BARRIER; PARKINSON'S DISEASE; PET; ULTRASOUND.

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Conflict of interest statement

Competing interests: CG-S has received lecture honoraria from Exeltis, Zambon, Palex, Fundación ACE, and Società Italiana Parkinson e Disordini del Movimento, and reimbursement of travel expenses to attend a scientific conference from Boston Scientific. EN-V was supported in 2021 by a fellowship from the Movement Disorders Group of the Spanish Neurology Society (Sociedad Española de Neurología) granted by Zambon and has received honoraria for lectures from Zambon and Palex. MM has received lecture honoraria from Teva, Zambon, Palex, the Spanish Neurological Society and the International Parkinson and Movement Disorders Society. MM has received research grants from the Michael J Fox Foundation and from the Nemesio Diez Foundation. RM-F has received speaker honoraria from Insightec, Palex, Bial and Zambon and reimbursement of travel expenses to attend scientific conferences from Insightec, Palex and Bial. He has a consulting agreement with Treefrog Therapeutics. IR and GT are employees of Insightec Ltd that has developed and commercialises the ultrasound transducer employed in this study. JAO has been a member of the Advisory Board of Insightec Ltd (2021-2022). The other authors declare no competing interests.

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