ArticleBritish journal of pharmacology2017
Widespread brain distribution and activity following i.c.v. infusion of anti-β-secretase (BACE1) in nonhuman primates.
Article in British journal of pharmacology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 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.
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Who cites it
26 citing papers in PubMed, 49 citations in OpenAlex.
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- Affibody Molecules Intended for Receptor-Mediated Transcytosis via the Transferrin Receptor.Pharmaceuticals (Basel, Switzerland) · 2023Article
- Novel Developments to Enable Treatment of CNS Diseases with Targeted Drug Delivery.Pharmaceutics · 2023Review
- Receptor-mediated drug delivery of bispecific therapeutic antibodies through the blood-brain barrier.Frontiers in drug delivery · 2023Article
- Therapeutics of Alzheimer's Disease: Recent Developments.Antioxidants (Basel, Switzerland) · 2022Review
- Biodistribution Analysis of an Anti-EGFR Antibody in the Rat Brain: Validation of CSF Microcirculation as a Viable Pathway to Circumvent the Blood-Brain Barrier for Drug Delivery.Pharmaceutics · 2022Article
- A Historical Review of Brain Drug Delivery.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
- Therapeutic antibodies - natural and pathological barriers and strategies to overcome them.Pharmacology & therapeutics · 2022Review
- Translational Approaches for Brain Delivery of Biologics via Cerebrospinal Fluid.Clinical pharmacology and therapeutics · 2022Review
- The glymphatic hypothesis: the theory and the evidence.Fluids and barriers of the CNS · 2022Review
- Delivery of Therapeutic Agents to the Central Nervous System and the Promise of Extracellular Vesicles.Pharmaceutics · 2021Review
- A translational platform PBPK model for antibody disposition in the brain.Journal of pharmacokinetics and pharmacodynamics · 2019Article
- Blood-Brain Barrier and Delivery of Protein and Gene Therapeutics to Brain.Frontiers in aging neuroscience · 2019Article
Corrections and comments
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Authors and funding
28 authors at 7 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
background and purposeThe potential for therapeutic antibody treatment of neurological diseases is limited by poor penetration across the blood-brain barrier. I.c.v. delivery is a promising route to the brain; however, it is unclear how efficiently antibodies delivered i.c.v. penetrate the cerebrospinal spinal fluid (CSF)-brain barrier and distribute throughout the brain parenchyma. EXPERIMENTAL APPROACH: We evaluated the pharmacokinetics and pharmacodynamics of an inhibitory monoclonal antibody against β-secretase 1 (anti-BACE1) following continuous infusion into the left lateral ventricle of healthy adult cynomolgus monkeys. KEY
resultsAnimals infused with anti-BACE1 i.c.v. showed a robust and sustained reduction (~70%) of CSF amyloid-β (Aβ) peptides. Antibody distribution was near uniform across the brain parenchyma, ranging from 20 to 40 nM, resulting in a ~50% reduction of Aβ in the cortical parenchyma. In contrast, animals administered anti-BACE1 i.v. showed no significant change in CSF or cortical Aβ levels and had a low (~0.6 nM) antibody concentration in the brain. CONCLUSION AND IMPLICATIONS: I.c.v. administration of anti-BACE1 resulted in enhanced BACE1 target engagement and inhibition, with a corresponding dramatic reduction in CNS Aβ concentrations, due to enhanced brain exposure to antibody.
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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.