ArticleBiotechnology and bioengineering2014
Insulin receptor antibody-iduronate 2-sulfatase fusion protein: pharmacokinetics, anti-drug antibody, and safety pharmacology in Rhesus monkeys.
Article in Biotechnology and bioengineering, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
43 citing papers in PubMed, 107 citations in OpenAlex.
- Iduronate-2-sulfatase fused with anti-hTfR antibody, pabinafusp alfa, for MPS-II: A phase 2 trial in Brazil.Molecular therapy : the journal of the American Society of Gene Therapy · 2021Trial
- A Phase 2/3 Trial of Pabinafusp Alfa, IDS Fused with Anti-Human Transferrin Receptor Antibody, Targeting Neurodegeneration in MPS-II.Molecular therapy : the journal of the American Society of Gene Therapy · 2021Trial
- Iduronate-2-Sulfatase with Anti-human Transferrin Receptor Antibody for Neuropathic Mucopolysaccharidosis II: A Phase 1/2 Trial.Molecular therapy : the journal of the American Society of Gene Therapy · 2019Trial
- Rescue of neurologic disease in mucopolysaccharidosis type II mice via AAV-mediated liver delivery of brain-penetrating iduronate-2-sulfatase.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2025Article
- Crossing the Blood-Brain Barrier: Innovations in Receptor- and Transporter-Mediated Transcytosis Strategies.Pharmaceutics · 2025Review
- In vivo brain delivery of BBB-enabled iduronate 2-sulfatase in rats.Fluids and barriers of the CNS · 2025Article
- Receptor-mediated transcytosis for brain delivery of therapeutics: receptor classes and criteria.Frontiers in drug delivery · 2024Review
- Bringing enzymes to the proximity party.RSC chemical biology · 2023Review
- Neurodevelopmental status and adaptive behavior of pediatric patients with mucopolysaccharidosis II: a longitudinal observational study.Orphanet journal of rare diseases · 2023Observational
- Transferrin Receptor-Targeted Iduronate-2-sulfatase Penetrates the Blood-Retinal Barrier and Improves Retinopathy in Mucopolysaccharidosis II Mice.Molecular pharmaceutics · 2023Article
- Characterization of a HIR-Fab-IDS, Novel Iduronate 2-Sulfatase Fusion Protein for the Treatment of Neuropathic Mucopolysaccharidosis Type II (Hunter Syndrome).BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy · 2023Article
- Targeting the central nervous system in lysosomal storage diseases: Strategies to deliver therapeutics across the blood-brain barrier.Molecular therapy : the journal of the American Society of Gene Therapy · 2023Review
- Transferrin Aptamers Increase theBioconjugate chemistry · 2022Article
- Engineering antibody and protein therapeutics to cross the blood-brain barrier.Antibody therapeutics · 2022Review
- Drug delivery for neuronopathic lysosomal storage diseases: evolving roles of the blood brain barrier and cerebrospinal fluid.Metabolic brain disease · 2022Review
- Transport Mechanisms at the Blood-Brain Barrier and in Cellular Compartments of the Neurovascular Unit: Focus on CNS Delivery of Small Molecule Drugs.Pharmaceutics · 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
- Treatment of Neuronopathic Mucopolysaccharidoses with Blood-Brain Barrier-Crossing Enzymes: Clinical Application of Receptor-Mediated Transcytosis.Pharmaceutics · 2022Review
- Towards a translational physiologically-based pharmacokinetic (PBPK) model for receptor-mediated transcytosis of anti-transferrin receptor monoclonal antibodies in the central nervous system.Journal of pharmacokinetics and pharmacodynamics · 2022Article
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Mucopolysaccharidosis (MPS) Type II is caused by mutations in the gene encoding the lysosomal enzyme, iduronate 2-sulfatase (IDS). The majority of MPSII cases affect the brain. However, enzyme replacement therapy with recombinant IDS does not treat the brain, because IDS is a large molecule drug that does not cross the blood-brain barrier (BBB). To enable BBB penetration, IDS has been re-engineered as an IgG-IDS fusion protein, where the IgG domain is a 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 the HIRMAb domain of the fusion protein acts as a molecular Trojan horse to ferry the fused IDS into brain from blood. The present study reports on the first safety pharmacology and pharmacokinetics study of the HIRMAb-IDS fusion protein. Juvenile male Rhesus monkeys were infused intravenously (IV) weekly for 26 weeks with 0, 3, 10, or 30 mg/kg of the HIRMAb-IDS fusion protein. The plasma clearance of the fusion protein followed a linear pharmacokinetics profile, which was equivalent either with measurements of the plasma concentration of immunoreactive HIRMAb-IDS fusion protein, or with assays of plasma IDS enzyme activity. Anti-drug antibody (ADA) titers were monitored monthly, and the ADA response was primarily directed against the variable region of the HIRMAb domain of the fusion protein. No infusion related reactions or clinical signs of immune response were observed during the course of the study. A battery of safety pharmacology, clinical chemistry, and tissue histopathology showed no signs of adverse events, and demonstrate the safety profile of chronic treatment of primates with 3-30 mg/kg weekly IV infusion doses of the HIRMAb-IDS 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.