ArticleDrug metabolism and disposition: the biological fate of chemicals2011
Brain-penetrating tumor necrosis factor decoy receptor in the mouse.
Article in Drug metabolism and disposition: the biological fate of chemicals, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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
24 citing papers in PubMed, 66 citations in OpenAlex.
- Antibody-Based Biologics for CNS Disorders.Antibodies (Basel, Switzerland) · 2026Review
- Brain Delivery of Antibody-Derived Biologicals for Alzheimer's Disease: An Updated Narrative Review.Antibodies (Basel, Switzerland) · 2026Review
- Modulation of hippocampal protein expression by a brain penetrant biologic TNF-α inhibitor in the 3xTg Alzheimer's disease mice.Journal of translational medicine · 2024Article
- Treatment of Parkinson's disease with biologics that penetrate the blood-brain barrier via receptor-mediated transport.Frontiers in aging neuroscience · 2023Review
- Efficacy and Safety of a Brain-Penetrant Biologic TNF-α Inhibitor in Aged APP/PS1 Mice.Pharmaceutics · 2022Article
- Engineering antibody and protein therapeutics to cross the blood-brain barrier.Antibody therapeutics · 2022Review
- A Historical Review of Brain Drug Delivery.Pharmaceutics · 2022Review
- Biologic TNF-α inhibitors reduce microgliosis, neuronal loss, and tau phosphorylation in a transgenic mouse model of tauopathy.Journal of neuroinflammation · 2021Article
- Activation of PPAR-β/δ Attenuates Brain Injury by Suppressing Inflammation and Apoptosis in a Collagenase-Induced Intracerebral Hemorrhage Mouse Model.Neurochemical research · 2020Article
- Post-stroke inflammation-target or tool for therapy?Acta neuropathologica · 2019Review
- Blood-Brain Barrier and Delivery of Protein and Gene Therapeutics to Brain.Frontiers in aging neuroscience · 2019Article
- Transcytosis to Cross the Blood Brain Barrier, New Advancements and Challenges.Frontiers in neuroscience · 2018Review
- Article
- Tumor necrosis factor α Inhibition for Alzheimer's Disease.Journal of central nervous system disease · 2017Review
- Excess cerebral TNF causing glutamate excitotoxicity rationalizes treatment of neurodegenerative diseases and neurogenic pain by anti-TNF agents.Journal of neuroinflammation · 2016Review
- Targeting receptor-mediated transport for delivery of biologics across the blood-brain barrier.Annual review of pharmacology and toxicology · 2015Review
- A Neurologist's Guide to TNF Biology and to the Principles behind the Therapeutic Removal of Excess TNF in Disease.Neural plasticity · 2015Review
- Agile delivery of protein therapeutics to CNS.Journal of controlled release : official journal of the Controlled Release Society · 2014Review
- Pharmacokinetics and brain uptake of an IgG-TNF decoy receptor fusion protein following intravenous, intraperitoneal, and subcutaneous administration in mice.Molecular pharmaceutics · 2013Article
- New hope for survivors of stroke and traumatic brain injury.CNS drugs · 2012Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
Biologic tumor necrosis factor inhibitors (TNFIs) include TNF decoy receptors (TNFRs). TNFα plays a pathologic role in both acute and chronic brain disease. However, biologic TNFIs cannot be developed as brain therapeutics because these large molecule drugs do not cross the blood-brain barrier (BBB). To enable penetration of the brain via receptor-mediated transport, the human TNFR type II was re-engineered as an IgG fusion protein, where the IgG part is a chimeric monoclonal antibody (MAb) against the mouse transferrin receptor (TfR), and this fusion protein is designated cTfRMAb-TNFR. The cTfRMAb part of the fusion protein acts as a molecular Trojan horse to ferry the TNFR across the BBB via transport on the endogenous BBB TfR. cTfRMAb-TNFR was expressed by stably transfected Chinese hamster ovary cells and purified by affinity chromatography to homogeneity on electrophoretic gels. The fusion protein reacted with antibodies to both mouse IgG and the human TNFR and bound TNFα with high affinity (K(d) = 96 ± 34 pM). cTfRMAb-TNFR was rapidly transported into mouse brain in vivo after intravenous administration, and the brain uptake of the fusion protein was 2.8 ± 0.5% of injected dose per gram of brain, which is >45-fold higher than the brain uptake of an IgG that does not recognize the mouse TfR. This new IgG-TNFR fusion protein can be tested in mouse models of brain diseases in which TNFα plays a pathologic role.
Indexed as
Identifiers
What OpenQuestion holds
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.