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

<p><span><span><span><span><span><span><span><span><span><span><span>MR-guided focused ultrasound (MRgFUS), in combination with intravenous microbubble administration, <span><span>has been</span></span> 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 <span><span>initiated a prospective, single-arm, non-randomized, proof-of-concept, safety and feasibility</span></span> phase I clinical trial <span><span>(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,</span></span> targeting the right parieto-occipito-temporal cortex where cortical pathology is foremost in this clinical state. <span><span>Changes in </span></span><span><span>β</span></span><span><span>-</span></span><span><span>amyloid burden, brain  metabolism after treatments and neuropsychological assessments, were analyzed as exploratory measurements.</span></span> <span><span>Five patients were recruited from October 2018 until May 2019, and</span></span> received two <span><span>treatment</span></span> sessions separated by 2-3 weeks. <span><span>The results are set out in a descriptive manner.</span></span> Overall, this procedure was feasible and reversible with no serious clinical or radiological side effects. <span><span>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.</span></span> 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 <span><span>performed</span></span> repeatedly. This study provides encouragement for the concept of BBB opening for drug delivery to treat dementia in PD and other neurodegenerative disorders.</span></span></span></span></span></span></span></span></span></span></span></p>