ArticleMolecular therapy : the journal of the American Society of Gene Therapy2018
TLR4-Binding DNA Aptamers Show a Protective Effect against Acute Stroke in Animal Models.
Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT05569720 (First in Human Clinical Trial to Compare Safety and Tolerability Between Intravenous Infusions and Bolus Intravenous Inhection of ApTOLL in Healthy Volunteers), which is not on this map. Cited by 34 papers, 1 of them a synthesis that pooled it.
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.
First in Human Clinical Trial to Compare Safety and Tolerability Between Intravenous Infusions and Bolus Intravenous Inhection of ApTOLL in Healthy Volunteers
Who cites it
34 citing papers in PubMed, 1 synthesis or guideline pooled it, 69 citations in OpenAlex.
- Role of Adaptor Protein Myeloid Differentiation 88 (MyD88) in Post-Subarachnoid Hemorrhage Inflammation: A Systematic Review.International journal of molecular sciences · 2021Pooled it
- Aptamer-based inhibition of MNK1 reduces pancreatic ductal adenocarcinoma growth by targeting cancer stem cells.Journal of biomedical science · 2026Article
- Serum Neurofilament Light Chain Predicts Stroke Outcome and is a Potential Marker for Treatment Effects of Neural Stem Cell-derived Extracellular Vesicles in a Rat Stroke Model.Translational stroke research · 2026Article
- Generation of aptamers for the selective detection and neutralization of soluble lymphotoxin alpha.Molecular therapy. Nucleic acids · 2026Article
- Targeting olfactory receptor OR2AT4: An innovative aptamer-based treatment for hair growth promotion.Molecular therapy. Nucleic acids · 2025Article
- Clinical trial to compare safety and tolerability between intravenous infusion and bolus intravenous injection of ApTOLL in healthy volunteers.Molecular therapy. Nucleic acids · 2025Article
- Extracellular cold-inducible RNA-binding protein in CNS injury: molecular insights and therapeutic approaches.Journal of neuroinflammation · 2025Review
- The prospective approach for aptamers applied in the treatment and molecular diagnostics of ischemic stroke.Frontiers in pharmacology · 2025Review
- Dynamic mechanisms and targeted interventions in cerebral ischemia-reperfusion injury: pathological cascade from ischemia to reperfusion and promising therapeutic strategies.Frontiers in neuroscience · 2025Review
- Programmatically activated DNA hydrogel microcapsules for precision therapy in inflammatory bowel disease.Theranostics · 2025Article
- Gut Microbiota, Bacterial Translocation, and Stroke: Current Knowledge and Future Directions.Biomedicines · 2024Review
- Ischemia/reperfusion injury in acute human and experimental stroke: focus on thrombo-inflammatory mechanisms and treatments.Neurological research and practice · 2024Review
- Cerebroprotective Effects of the TLR4-Binding DNA Aptamer ApTOLL in a Rat Model of Ischemic Stroke and Thrombectomy Recanalization.Pharmaceutics · 2024Article
- Aptamer Technologies in Neuroscience, Neuro-Diagnostics and Neuro-Medicine Development.Molecules (Basel, Switzerland) · 2024Review
- Immune-Neurovascular Interactions in Experimental Perinatal and Childhood Arterial Ischemic Stroke.Stroke · 2024Review
- Neuroprotection during Thrombectomy for Acute Ischemic Stroke: A Review of Future Therapies.International journal of molecular sciences · 2024Review
- Brain FADE syndrome: the final common pathway of chronic inflammation in neurological disease.Frontiers in immunology · 2024Review
- Inhaled aptamer therapy: A hopeful therapy for lung disease.Molecular therapy. Nucleic acids · 2023Article
- Exosomal ZEB1 Derived from Neural Stem Cells Reduces Inflammation Injury in OGD/R-Treated Microglia via the GPR30-TLR4-NF-κB Axis.Neurochemical research · 2023Article
- Neuroprotective Strategies for Ischemic Stroke-Future Perspectives.International journal of molecular sciences · 2023Review
Corrections and comments
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Authors and funding
15 authors at 5 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Since Toll-like receptor 4 (TLR4) mediates brain damage after stroke, development of TLR4 antagonists is a promising therapeutic strategy for this disease. Our aim was to generate TLR4-blocking DNA aptamers to be used for stroke treatment. From a random oligonucleotide pool, we identified two aptamers (ApTLR#1R, ApTLR#4F) with high affinity for human TLR4 by systematic evolution of ligands by exponential enrichment (SELEX). Optimized truncated forms (ApTLR#1RT, ApTLR#4FT) were obtained. Our data demonstrate specific binding of both aptamers to human TLR4 as well as a TLR4 antagonistic effect. ApTLR#4F and ApTLR#4FT showed a long-lasting protective effect against brain injury induced by middle cerebral artery occlusion (MCAO), an effect that was absent in TLR4-deficient mice. Similar effects were obtained in other MCAO models, including in rat. Additionally, efficacy of ApTLR#4FT in a model of brain ischemia-reperfusion in rat supports the use of this aptamer in patients undergoing artery recanalization induced by pharmacological or mechanical interventions. The absence of major toxicology aspects and the good safety profile of the aptamers further encourage their future clinical positioning for stroke therapy and possibly other diseases in which TLR4 plays a deleterious role.
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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.