PMID- 33536430 OWN - NLM STAT- MEDLINE DCOM- 20210222 LR - 20210222 IS - 2041-1723 (Electronic) IS - 2041-1723 (Linking) VI - 12 IP - 1 DP - 2021 Feb 3 TI - Blood-brain barrier opening with focused ultrasound in Parkinson's disease dementia. PG - 779 LID - 10.1038/s41467-021-21022-9 [doi] LID - 779 AB - 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. FAU - Gasca-Salas, Carmen AU - Gasca-Salas C AUID- ORCID: 0000-0001-7411-8106 AD - HM CINAC, Fundacion HM Hospitales de Madrid, University Hospital HM Puerta del Sur. CEU-San Pablo University, Mostoles, Madrid, Spain. AD - Network Center for Biomedical Research on Neurodegenerative Diseases (CIBERNED), Instituto Carlos III, Madrid, Spain. FAU - Fernandez-Rodriguez, Beatriz AU - Fernandez-Rodriguez B AD - HM CINAC, Fundacion HM Hospitales de Madrid, University Hospital HM Puerta del Sur. CEU-San Pablo University, Mostoles, Madrid, Spain. FAU - Pineda-Pardo, Jose A AU - Pineda-Pardo JA AUID- ORCID: 0000-0002-8776-0031 AD - HM CINAC, Fundacion HM Hospitales de Madrid, University Hospital HM Puerta del Sur. CEU-San Pablo University, Mostoles, Madrid, Spain. AD - Network Center for Biomedical Research on Neurodegenerative Diseases (CIBERNED), Instituto Carlos III, Madrid, Spain. FAU - Rodriguez-Rojas, Rafael AU - Rodriguez-Rojas R AUID- ORCID: 0000-0002-2903-199X AD - HM CINAC, Fundacion HM Hospitales de Madrid, University Hospital HM Puerta del Sur. CEU-San Pablo University, Mostoles, Madrid, Spain. AD - Network Center for Biomedical Research on Neurodegenerative Diseases (CIBERNED), Instituto Carlos III, Madrid, Spain. FAU - Obeso, Ignacio AU - Obeso I AD - HM CINAC, Fundacion HM Hospitales de Madrid, University Hospital HM Puerta del Sur. CEU-San Pablo University, Mostoles, Madrid, Spain. AD - Network Center for Biomedical Research on Neurodegenerative Diseases (CIBERNED), Instituto Carlos III, Madrid, Spain. FAU - Hernandez-Fernandez, Frida AU - Hernandez-Fernandez F AD - HM CINAC, Fundacion HM Hospitales de Madrid, University Hospital HM Puerta del Sur. CEU-San Pablo University, Mostoles, Madrid, Spain. AD - Department of Nursing, Universidad Europea de Madrid. Faculty of Biomedical and Health Sciences, Villaviciosa de Odon, Madrid, Spain. FAU - Del Alamo, Marta AU - Del Alamo M AD - HM CINAC, Fundacion HM Hospitales de Madrid, University Hospital HM Puerta del Sur. CEU-San Pablo University, Mostoles, Madrid, Spain. AD - Network Center for Biomedical Research on Neurodegenerative Diseases (CIBERNED), Instituto Carlos III, Madrid, Spain. FAU - Mata, David AU - Mata D AD - HM CINAC, Fundacion HM Hospitales de Madrid, University Hospital HM Puerta del Sur. CEU-San Pablo University, Mostoles, Madrid, Spain. AD - Network Center for Biomedical Research on Neurodegenerative Diseases (CIBERNED), Instituto Carlos III, Madrid, Spain. FAU - Guida, Pasqualina AU - Guida P AD - HM CINAC, Fundacion HM Hospitales de Madrid, University Hospital HM Puerta del Sur. CEU-San Pablo University, Mostoles, Madrid, Spain. AD - Network Center for Biomedical Research on Neurodegenerative Diseases (CIBERNED), Instituto Carlos III, Madrid, Spain. FAU - Ordas-Bandera, Carlos AU - Ordas-Bandera C AD - Hospital Universitario Rey Juan Carlos, Mostoles, Madrid, Spain. FAU - Montero-Roblas, J Ignacio AU - Montero-Roblas JI AD - Intensive care Unit, University Hospital HM Puerta del Sur, Mostoles, Madrid, Spain. FAU - Martinez-Fernandez, Raul AU - Martinez-Fernandez R AD - HM CINAC, Fundacion HM Hospitales de Madrid, University Hospital HM Puerta del Sur. CEU-San Pablo University, Mostoles, Madrid, Spain. AD - Network Center for Biomedical Research on Neurodegenerative Diseases (CIBERNED), Instituto Carlos III, Madrid, Spain. FAU - Foffani, Guglielmo AU - Foffani G AD - HM CINAC, Fundacion HM Hospitales de Madrid, University Hospital HM Puerta del Sur. CEU-San Pablo University, Mostoles, Madrid, Spain. AD - Network Center for Biomedical Research on Neurodegenerative Diseases (CIBERNED), Instituto Carlos III, Madrid, Spain. AD - Hospital Nacional de Paraplejicos, Toledo, Spain. FAU - Rachmilevitch, Itay AU - Rachmilevitch I AD - Insightec LTD, Haifa, Israel. FAU - Obeso, Jose A AU - Obeso JA AD - HM CINAC, Fundacion HM Hospitales de Madrid, University Hospital HM Puerta del Sur. CEU-San Pablo University, Mostoles, Madrid, Spain. jobeso.hmcinac@hmhospitales.com. AD - Network Center for Biomedical Research on Neurodegenerative Diseases (CIBERNED), Instituto Carlos III, Madrid, Spain. jobeso.hmcinac@hmhospitales.com. LA - eng SI - Dryad/10.5061/dryad.0k6djh9zk SI - ClinicalTrials.gov/NCT03608553 PT - Clinical Trial, Phase I PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20210203 PL - England TA - Nat Commun JT - Nature communications JID - 101528555 RN - 0 (Contrast Media) SB - IM MH - Aged MH - Alzheimer Disease/diagnostic imaging/therapy MH - Blood-Brain Barrier/*diagnostic imaging/metabolism MH - Brain Neoplasms/diagnostic imaging/therapy MH - Contrast Media MH - Dementia/*diagnostic imaging/therapy MH - Feasibility Studies MH - Humans MH - Magnetic Resonance Imaging/methods MH - Male MH - Microbubbles MH - Outcome Assessment, Health Care/methods MH - Parkinson Disease/*diagnostic imaging/therapy MH - Positron-Emission Tomography/methods MH - Prospective Studies MH - Ultrasonography/*methods PMC - PMC7859400 COIS- JAO has attended board meetings of Insightec and received an honorarium. RMF received honoraria for lecturing and payment to attend scientific meetings from Insightec. The other authors declare no competing interests. EDAT- 2021/02/05 06:00 MHDA- 2021/02/23 06:00 PMCR- 2021/02/03 CRDT- 2021/02/04 05:43 PHST- 2020/02/11 00:00 [received] PHST- 2020/12/11 00:00 [accepted] PHST- 2021/02/04 05:43 [entrez] PHST- 2021/02/05 06:00 [pubmed] PHST- 2021/02/23 06:00 [medline] PHST- 2021/02/03 00:00 [pmc-release] AID - 10.1038/s41467-021-21022-9 [pii] AID - 21022 [pii] AID - 10.1038/s41467-021-21022-9 [doi] PST - epublish SO - Nat Commun. 2021 Feb 3;12(1):779. doi: 10.1038/s41467-021-21022-9.