Brain-Targeted Liposomes Loaded with Monoclonal Antibodies Reduce Alpha-Synuclein Aggregation and Improve Behavioral Symptoms of Parkinson’s Disease

Monoclonal antibodies (mAbs) hold promise for treating Parkinson’s disease (PD), but their therapeutic use is hindered by poor delivery to the brain. In this study, we demonstrate that brain-targeted liposomes (BTL) enhance the delivery of mAbs across the blood-brain-barrier (BBB) and into neurons, thereby improving the intracellular and extracellular treatment of the PD brain. BTL were decorated with transferrin to improve brain targeting through overexpressed transferrin-receptors on the BBB during PD. The BTL were loaded with SynO4, a mAb that inhibits alpha-synuclein (AS) aggregation, a pathological hallmark of PD.

We show that 100-nm BTL cross human BBB models intact and were taken up by primary neurons. Inside the neurons, SynO4 is released from the nanoparticles and binds to its target, thereby reducing AS aggregation and increasing neuronal viability. In-vivo, intravenous administration of BTL led to a 7-fold increase of mAbs in brain cells, reducing AS aggregation and neuroinflammation. In addition, BTL treatments improved behavioral motor function and learning ability in mice, with a favorable safety profile. Targeted nanotechnologies are promising platforms for delivering medicines to treat brain neurodegeneration.

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Brain-Targeted Liposomes Loaded with Monoclonal Antibodies Reduce Alpha-Synuclein Aggregation and Improve Behavioral Symptoms of Parkinson’s Disease, Mor Sela, Maria Poley, Patricia Mora-Raimundo, Shaked Kagan, Aviram Avital, Maya Kaduri, Gal Chen, Omer Adir, Adi Rozencweig, Yfat Weiss, Ofir Sade, Yael Leichtmann-Bardoogo, Lilach Simchi, Shlomit Age-Mizrachi, Batia Bell, Yoel Yeretz-Peretz, Aviv Zaid Or, Ashwani Choudhary, Idan Rosh, Diogo Cordeiro, Stav Choen-Adiv, Yevgeny Berdichevsky, Anas Ode, Jeny Shklover, Janna Shainsky-Roitman, Joshua E. Schroeder, Dov Hershkovitz, Peleg Hasson, Avraham Ashkenazi, Shani Stern, Tal Laviv, Ayal Ben-Zvi, Avi Avital, Uri Ashery, Ben M. Maoz, Avi Schroeder, First published: 27 September 2023 https://doi.org/10.1002/adma.202304654