ArticlePharmaceutics2022
Reduction of αSYN Pathology in a Mouse Model of PD Using a Brain-Penetrating Bispecific Antibody.
Article in Pharmaceutics, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers, 1 of them a synthesis that pooled it.
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Who cites it
18 citing papers in PubMed, 1 synthesis or guideline pooled it, 26 citations in OpenAlex.
- Are Therapies That Target α-Synuclein Effective at Halting Parkinson's Disease Progression? A Systematic Review.International journal of molecular sciences · 2023Pooled it
- Early glymphatic failure in AppNL-F knock-in mice is linked to parenchymal border macrophages loss.Brain : a journal of neurology · 2026Article
- Incidental vs. Engineered Nanoparticles in Alzheimer's and Parkinson's Disease: Pathological Pathways and Therapeutic Interventions.Nano research · 2025Article
- Bispecific brain-penetrant antibodies for treatment of Alzheimer's disease.The journal of prevention of Alzheimer's disease · 2025Review
- A brain-penetrant bispecific antibody lowers oligomeric alpha-synuclein and activates microglia in a mouse model of alpha-synuclein pathology.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2025Article
- The Evolving Applications of Bispecific Antibodies: Reaping the Harvest of Early Sowing and Planting New Seeds.BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy · 2025Review
- Investigation of the Impact of the H310A FcRn Region Mutation onMolecular imaging and biology · 2024Article
- ENGINEERED NANOBODIES WITH PROGRAMMABLE TARGET ANTIGEN PROTEOLYSIS (PTAP) FUSIONS REGULATE INTRACELLULAR ALPHA-SYNUCLEIN IN VITRO AND IN VIVO.Research square · 2024Article
- Synthesis and evaluation of fluorine-18 labelled tetrazines as pre-targeting imaging agents for PET.EJNMMI radiopharmacy and chemistry · 2024Article
- AAV-mediated expression of a new conformational anti-aggregated α-synuclein antibody prolongs survival in a genetic model of α-synucleinopathies.NPJ Parkinson's disease · 2023Article
- Long-term effects of immunotherapy with a brain penetrating Aβ antibody in a mouse model of Alzheimer's disease.Alzheimer's research & therapy · 2023Article
- Translational molecular imaging and drug development in Parkinson's disease.Molecular neurodegeneration · 2023Review
- Receptor-mediated drug delivery of bispecific therapeutic antibodies through the blood-brain barrier.Frontiers in drug delivery · 2023Article
- Treatment of Parkinson's disease with biologics that penetrate the blood-brain barrier via receptor-mediated transport.Frontiers in aging neuroscience · 2023Review
- Bispecific antibodies revolutionizing breast cancer treatment: a comprehensive overview.Frontiers in immunology · 2023Review
- Advanced Blood-Brain Barrier Drug Delivery.Pharmaceutics · 2022Article
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Corrections and comments
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Authors and funding
10 authors at 2 institutions in 3 countries.
Funding
Abstract
Immunotherapy targeting aggregated alpha-synuclein (αSYN) is a promising approach for the treatment of Parkinson's disease. However, brain penetration of antibodies is hampered by their large size. Here, RmAbSynO2-scFv8D3, a modified bispecific antibody that targets aggregated αSYN and binds to the transferrin receptor for facilitated brain uptake, was investigated to treat αSYN pathology in transgenic mice. Ex vivo analyses of the blood and brain distribution of RmAbSynO2-scFv8D3 and the unmodified variant RmAbSynO2, as well as in vivo analyses with microdialysis and PET, confirmed fast and efficient brain uptake of the bispecific format. In addition, intravenous administration was shown to be superior to intraperitoneal injections in terms of brain uptake and distribution. Next, aged female αSYN transgenic mice (L61) were administered either RmAbSynO2-scFv8D3, RmAbSynO2, or PBS intravenously three times over five days. Levels of TBS-T soluble aggregated αSYN in the brain following treatment with RmAbSynO2-scFv8D3 were decreased in the cortex and midbrain compared to RmAbSynO2 or PBS controls. Taken together, our results indicate that facilitated brain uptake of αSYN antibodies can improve treatment of αSYN pathology.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.