biostudies-literatureSela MIsrael National Institute for Health Policy ResearchEuropean Research CouncilIsrael Science FoundationPhospholipid Research CenterTeva Pharmaceutical IndustriesMichael J. Fox Foundation for Parkinson's Researche2304654https://www.ebi.ac.uk/biostudies/studies/S-EPMC7615408biostudies-literatureUnknown35(51)Monoclonal antibodies (mAbs) hold promise in treating Parkinson's disease (PD), although poor delivery to the brain hinders their therapeutic application. In the current study, it is demonstrated that brain-targeted liposomes (BTL) enhance the delivery of mAbs across the blood-brain-barrier (BBB) and into neurons, thereby allowing the intracellular and extracellular treatment of the PD brain. BTL are decorated with transferrin to improve brain targeting through overexpressed transferrin-receptors on the BBB during PD. BTL are loaded with SynO4, a mAb that inhibits alpha-synuclein (AS) aggregation, a pathological hallmark of PD. It is shown that 100-nm BTL cross human BBB models intact and are taken up by primary neurons. Within neurons, SynO4 is released from the nanoparticles and bound toAdvanced materials (Deerfield Beach, Fla.)Brain-Targeted Liposomes Loaded with Monoclonal Antibodies Reduce Alpha-Synuclein Aggregation and Improve Behavioral Symptoms in Parkinson's Disease.PMC76154081010890091881/211010401282248/198517651384/21MJFF‐0224071R21AG074846‐01A12141/201934/23ASC‐2018‐062/1‐12359/23Choudhary AWeiss YKagan SSchroeder JEAvital AAdir OOdeh ABerdichevsky YYeretz-Peretz YAga-Mizrachi SBen-Zvi AKaduri MHershkovitz DAshery UHasson PSchroeder ARozencweig AMora-Raimundo PBell BRosh IShklover JShainsky-Roitman JAshkenazi AChen GSimchi LLaviv TStern SSela MPoley MLeichtmann-Bardoogo YCordeiro DSade OMaoz BMOr AZCohen-Adiv SfalseBrain-Targeted Liposomes Loaded with Monoclonal Antibodies Reduce Alpha-Synuclein Aggregation and Improve Behavioral Symptoms in Parkinson's Disease.Monoclonal antibodies (mAbs) hold promise in treating Parkinson's disease (PD), although poor delivery to the brain hinders their therapeutic application. In the current study, it is demonstrated that brain-targeted liposomes (BTL) enhance the delivery of mAbs across the blood-brain-barrier (BBB) and into neurons, thereby allowing the intracellular and extracellular treatment of the PD brain. BTL are decorated with transferrin to improve brain targeting through overexpressed transferrin-receptors on the BBB during PD. BTL are loaded with SynO4, a mAb that inhibits alpha-synuclein (AS) aggregation, a pathological hallmark of PD. It is shown that 100-nm BTL cross human BBB models intact and are taken up by primary neurons. Within neurons, SynO4 is released from the nanoparticles and bound to2023-01-01T00:00:00Z2023 Dec2025-04-18T16:07:59.69Z2025-04-07T03:07:40.357ZS-EPMC76154083775392810.1002/adma.202304654