ArticleBiotechnology and bioengineering2013
Pharmacokinetics and brain uptake in the rhesus monkey of a fusion protein of arylsulfatase a and a monoclonal antibody against the human insulin receptor.
Article in Biotechnology and bioengineering, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed, 66 citations in OpenAlex.
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- Are TrkB receptor agonists the right tool to fulfill the promises for a therapeutic value of the brain-derived neurotrophic factor?Neural regeneration research · 2024Review
- Receptor-mediated drug delivery of bispecific therapeutic antibodies through the blood-brain barrier.Frontiers in drug delivery · 2023Article
- Immunogenicity of MultiTEP platform technology-based Tau vaccine in non-human primates.NPJ vaccines · 2022Article
- Engineering antibody and protein therapeutics to cross the blood-brain barrier.Antibody therapeutics · 2022Review
- Overcoming the blood-brain barrier for the therapy of malignant brain tumor: current status and prospects of drug delivery approaches.Journal of nanobiotechnology · 2022Review
- IgG Fusion Proteins for Brain Delivery of Biologics via Blood-Brain Barrier Receptor-Mediated Transport.Pharmaceutics · 2022Review
- A Historical Review of Brain Drug Delivery.Pharmaceutics · 2022Review
- Considerations When Developing Blood-Brain Barrier Crossing Drug Delivery Technology.Handbook of experimental pharmacology · 2022Review
- Novel Brain-Penetrating Single Chain Antibodies Directed Against 3RTau for the Treatment of Alzheimer's Disease and Related Dementias.Methods in molecular biology (Clifton, N.J.) · 2022Article
- Mathematical Models of Blood-Brain Barrier Transport of Monoclonal Antibodies Targeting the Transferrin Receptor and the Insulin Receptor.Pharmaceuticals (Basel, Switzerland) · 2021Article
- Brain Delivery of Nanomedicines: Trojan Horse Liposomes for Plasmid DNA Gene Therapy of the Brain.Frontiers in medical technology · 2020Review
- Metachromatic Leukodystrophy: Diagnosis, Modeling, and Treatment Approaches.Frontiers in medicine · 2020Review
- Targeted enzyme delivery systems in lysosomal disorders: an innovative form of therapy for mucopolysaccharidosis.Cellular and molecular life sciences : CMLS · 2019Review
- Immunotherapy targeting toll-like receptor 2 alleviates neurodegeneration in models of synucleinopathy by modulating α-synuclein transmission and neuroinflammation.Molecular neurodegeneration · 2018Article
- Selective targeting of 3 repeat Tau with brain penetrating single chain antibodies for the treatment of neurodegenerative disorders.Acta neuropathologica · 2018Article
- Strategies for Enhancing the Permeation of CNS-Active Drugs through the Blood-Brain Barrier: A Review.Molecules (Basel, Switzerland) · 2018Review
- Enzymes as Immunotherapeutics.Bioconjugate chemistry · 2018Review
- Transcytosis to Cross the Blood Brain Barrier, New Advancements and Challenges.Frontiers in neuroscience · 2018Review
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
Metachromatic leukodystrophy (MLD) is a lysosomal storage disorder of the brain caused by mutations in the gene encoding the lysosomal sulfatase, arylsulfatase A (ASA). It is not possible to treat the brain in MLD with recombinant ASA, because the enzyme does not cross the blood-brain barrier (BBB). In the present investigation, a BBB-penetrating IgG-ASA fusion protein is engineered and expressed, where the ASA monomer is fused to the carboxyl terminus of each heavy chain of an engineered monoclonal antibody (MAb) against the human insulin receptor (HIR). The HIRMAb crosses the BBB via receptor-mediated transport on the endogenous BBB insulin receptor, and acts as a molecular Trojan horse to ferry the ASA into brain from blood. The HIRMAb-ASA is expressed in stably transfected Chinese hamster ovary cells grown in serum free medium, and purified by protein A affinity chromatography. The fusion protein retains high affinity binding to the HIR, EC50 = 0.34 ± 0.11 nM, and retains high ASA enzyme activity, 20 ± 1 units/mg. The HIRMAb-ASA fusion protein is endocytosed and triaged to the lysosomal compartment in MLD fibroblasts. The fusion protein was radio-labeled with the Bolton-Hunter reagent, and the [(125) I]-HIRMAb-ASA rapidly penetrates the brain in the Rhesus monkey following intravenous administration. Film and emulsion autoradiography of primate brain shows global distribution of the fusion protein throughout the monkey brain. These studies describe a new biological entity that is designed to treat the brain of humans with MLD following non-invasive, intravenous infusion of an IgG-ASA fusion protein.
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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.