Focused ultrasound enhanced antibody delivery for the treatment of Parkinson's Disease

Treatment of neurological disorders is partly impeded by the size of large pharmacological agents which are thereby unable to bypass the blood brain barrier. Focused ultrasound in conjunction with systemically administered microbubbles has been shown to safely noninvasively and transiently open the BBB allowing the passage of large biomolecules to the brain parenchyma through the otherwise impermeable barrier. This pilot study assessed the feasibility of FUS mediated delivery of an anti alpha synuclein monoclonal antibody in Parkinsons disease mouse models that exhibit aggregates. Mice underwent FUS on a weekly basis over the course of 2 to 3 weeks followed by a one month survival period. MRI and microscopy were performed to confirm BBB opening with FUS and visualize antibody delivery. Safety was assessed in vivo using passive cavitation detection and immunohistochemistry to evaluate microglial and astrocyte activity ex vivo. It was found that treatment sessions for multiple FUS sessions of targeted antibody delivery was feasible in alpha-synuclein models facilitating immunotherapeutics.