ArticlePharmaceutics2022
A Single Domain Shark Antibody Targeting the Transferrin Receptor 1 Delivers a TrkB Agonist Antibody to the Brain and Provides Full Neuroprotection in a Mouse Model of Parkinson's Disease.
Article in Pharmaceutics, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 29 citations in OpenAlex.
- Antibody-Based Biologics for CNS Disorders.Antibodies (Basel, Switzerland) · 2026Review
- Targeting Transferrin Receptor 1 for Enhancing Drug Delivery Through the Blood-Brain Barrier for Alzheimer's Disease.International journal of molecular sciences · 2025Review
- Comparative Radiotracing Quantifies Brain Cellular Uptake and Catabolism of Bispecific Antibodies Targeting Transferrin Receptor and CD98hc.ACS chemical neuroscience · 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
- A novel shark VNAR antibody-based immunotoxin targeting TROP-2 for cancer therapy.Acta pharmaceutica Sinica. B · 2024Article
- Screening and anti-angiogenesis activity of Chiloscyllium plagiosum anti-human VEGFR2 single-domain antibody.Clinical and experimental immunology · 2024Article
- Investigation of the Impact of the H310A FcRn Region Mutation onMolecular imaging and biology · 2024Article
- Transcytosis-Driven Treatment of Neurodegenerative Disorders by mRNA-Expressed Antibody-Transferrin Conjugates.Biomedicines · 2024Review
- The Role of Force Fields and Water Models in Protein Folding and Unfolding Dynamics.Journal of chemical theory and computation · 2024Article
- Recombinant Antibody Fragments for Immunotherapy of Parkinson's Disease.BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy · 2024Review
- Bispecific antibody shuttles targeting CD98hc mediate efficient and long-lived brain delivery of IgGs.Cell chemical biology · 2024Article
- Receptor-mediated transcytosis for brain delivery of therapeutics: receptor classes and criteria.Frontiers in drug delivery · 2024Review
- Recombinant Antibody Fragments for Neurological Disorders: An Update.Current neuropharmacology · 2024Review
- Single-domain antibodies and aptamers drive new opportunities for neurodegenerative disease research.Frontiers in immunology · 2024Review
- Structure and Dynamics Guiding Design of Antibody Therapeutics and Vaccines.Antibodies (Basel, Switzerland) · 2023Review
- Shark IgNAR: The Next Broad Application Antibody in Clinical Diagnoses and Tumor Therapies?Marine drugs · 2023Review
- CD98hc is a target for brain delivery of biotherapeutics.Nature communications · 2023Article
- Designing receptor agonists with enhanced pharmacokinetics by grafting macrocyclic peptides into fragment crystallizable regions.Nature biomedical engineering · 2023Article
- A novel shark single-domain antibody targeting OGT as a tool for detection and intracellular localization.Frontiers in immunology · 2023Article
- Receptor-mediated drug delivery of bispecific therapeutic antibodies through the blood-brain barrier.Frontiers in drug delivery · 2023Article
Corrections and comments
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Authors and funding
10 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Single domain shark antibodies that bind to the transferrin receptor 1 (TfR1) on brain endothelial cells have been used to shuttle antibodies and other cargos across the blood brain barrier (BBB) to the brain. For these studies the TXB4 brain shuttle was fused to a TrkB neurotrophin receptor agonist antibody. The TXB4-TrkB fusion retained potent agonist activity at its cognate receptor and after systemic administration showed a 12-fold increase in brain levels over the unmodified antibody. Only the TXB4-TrkB antibody fusion was detected within the brain and localized to TrkB positive cells in the cortex and tyrosine hydroxylase (TH) positive dopaminergic neurons in the substantia nigra pars compacta (SNc), where it was associated with activated ERK1/2 signaling. When tested in the 6-hydroxydopamine (6-OHDA) mouse model of Parkinson's disease (PD), TXB4-TrkB, but not the unmodified antibody, completely prevented the 6-OHDA induced death of TH positive neurons in the SNc. In conclusion, the fusion of the TXB4 brain shuttle allows a TrkB agonist antibody to reach neuroprotective concentrations in the brain parenchyma following systemic administration.
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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.