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Nigrostriatal blood-brain barrier opening in Parkinson’s disease
  1. Carmen Gasca-Salas1,2,3,
  2. José A Pineda-Pardo1,2,3,
  3. Marta Del Álamo1,2,
  4. Tamara Jiménez1,2,
  5. Clara Trompeta1,2,4,
  6. Gabriella Toltsis5,
  7. Lina Garcia-Cañamaque6,
  8. Beatriz Fernández-Rodríguez1,2,
  9. Michele Matarazzo1,2,3,
  10. Isabel Plaza de las Heras6,
  11. Elena Natera-Villalba1,2,
  12. Raúl Martínez-Fernández1,2,3,
  13. Alicia Duque7,
  14. Santiago Ruiz de Aguiar8,
  15. Javier Blesa1,2,3,9,
  16. Itay Rachmilevich5,
  17. José A Obeso1,2,3
  1. 1HM CINAC (Centro Integral de Neurociencias Abarca Campal), Hospital Universitario HM Puerta del Sur, HM Hospitales, Madrid, Spain
  2. 2Instituto de Investigación Sanitaria HM Hospitales, Madrid, Spain
  3. 3Centro de Investigacion Biomedica en Red sobre Enfermedades Neurodegenerativas, Madrid, Spain
  4. 4PhD Program in Health Sciences, University of Alcala de Henares, Alcalá de Henares, Madrid. Spain 28054, Alcalá de Henares, Spain
  5. 5InSightec Ltd, Tirat Carmel, Israel
  6. 6Nuclear Medicine Department. PET-MRI centre, Hospital Universitario HM Puerta del Sur, HM Hospitales, Madrid, Spain
  7. 7Neuroradiology Unit, Hospital Universitario HM Puerta del Sur, HM Hospitales, Madrid, Spain
  8. 8Medical Director, Hospital Universitario HM Puerta del Sur, HM Hospitales, Madrid, Spain
  9. 9Facultad HM de Ciencias de la Salud de la Universidad Camilo José Cela, Madrid, Spain
  1. Correspondence to Professor José A Obeso, HM CINAC (Centro Integral de Neurociencias Abarca Campal), Hospital Universitario HM Puerta del Sur, HM Hospitales, Madrid 28938, Spain; jobeso.hmcinac{at}hmhospitales.com

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.

  • PARKINSON'S DISEASE
  • BLOOD-BRAIN BARRIER
  • ULTRASOUND
  • PET

Data availability statement

Raw clinical and imaging data are not publicly available due to patient privacy or ethical restrictions. The data generated during this study are available from the corresponding author upon reasonable request.

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Data availability statement

Raw clinical and imaging data are not publicly available due to patient privacy or ethical restrictions. The data generated during this study are available from the corresponding author upon reasonable request.

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Footnotes

  • X @matarazzomd

  • Contributors Conception and design: CG-S, JAP-P, JB, JAO. Study organisation: CG-S, JAP-P, MDA, TJ, SRdA, JAO. Patient screening, recruitment and evaluation: CG-S, CT, BF-R, MM, EN-V, RM-F. Focused ultrasound procedure: CG-S, JAP-P, MDA, TJ, GT, IR, JAO. Imaging data collection: JAP-P, LG-C, IPdlH, AD. Data curation: CG-S, JAP-P, CT, JAO. Drafting of the work: CG-S, JAP-P, JAO. Revising the work for important intellectual content and final approval: all authors.

  • Funding Ministerio de Educación y Ciencias (Grant number PID2019 111045RB-I00 to JAO), Ministerio de Ciencia e Innovación y Universidades (Grant number PID2021-127800OA-I00 to JAPP), MAPFRE Foundation (JAO), Instituto de Salud Carlos III Miguel Servet Program (CP19/00200 to JB) and FIS (PI23/00672 to JB).

  • 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.

  • Provenance and peer review Not commissioned; externally peer reviewed.

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