ArticleMolecular therapy : the journal of the American Society of Gene Therapy2021
Systemic delivery of antagomirs during blood-brain barrier disruption is disease-modifying in experimental epilepsy.
Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 39 citations in OpenAlex.
- MiRNA Dysregulation in Epilepsy: Bridging Molecular Mechanisms and Therapeutic Innovation.Molecular neurobiology · 2026Review
- Identification of EEG features during status epilepticus for prediction of emergent epilepsy phenotype in the mouse intra-amygdala kainic acid model using supervised learning.IBRO neuroscience reports · 2026Article
- Attenuated Single Neuron and Network Hyperexcitability Following MicroRNA-134 Inhibition in Mice with Drug-Resistant Temporal Lobe Epilepsy.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2026Article
- Vascular and Neural Transcriptomics Reveal Stage-Dependent Pathways to Inflammation and Cognitive Dysfunction in a Rat Model of Hypertension.Journal of the American Heart Association · 2026Article
- Commonalities in gene expression and methylation changes across two rat models of acquired epilepsy.Scientific reports · 2026Article
- The Role of Blood-Brain Barrier Disruption in Epilepsy: Mechanisms and Consequences.Neurology international · 2025Review
- How Soon is Soon Enough? Consideration of Timing and Disease Etiology for microRNAs in Epilepsy.Epilepsy currents · 2025Review
- Pharmacogenetics of anti-seizure medications in Arab countries: a comprehensive review.Future science OA · 2025Review
- Potential for Therapeutic Alteration of the Underlying Biology of Epilepsy.Biomedicines · 2025Review
- The role of electroencephalography in epilepsy research-From seizures to interictal activity and comorbidities.Epilepsia · 2025Review
- Interictal blood-brain barrier dysfunction in piriform cortex of people with epilepsy.Annals of clinical and translational neurology · 2024Article
- Circulating miRNAs as Novel Clinical Biomarkers in Temporal Lobe Epilepsy.Non-coding RNA · 2024Review
- microRNA profilings identify plasma biomarkers and targets associated with pediatric epilepsy patients.Pediatric research · 2024Article
- Unveiling the hidden connection: the blood-brain barrier's role in epilepsy.Frontiers in neurology · 2024Review
- Review
- Brain cell-specific origin of circulating microRNA biomarkers in experimental temporal lobe epilepsy.Frontiers in molecular neuroscience · 2023Article
- MiR-324-5p inhibition after intrahippocampal kainic acid-inducedFrontiers in neurology · 2023Article
- Epigenetic genes and epilepsy - emerging mechanisms and clinical applications.Nature reviews. Neurology · 2022Review
- Article
- AntimiR targeting of microRNA-134 reduces seizures in a mouse model of Angelman syndrome.Molecular therapy. Nucleic acids · 2022Article
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Authors and funding
19 authors at 6 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Oligonucleotide therapies offer precision treatments for a variety of neurological diseases, including epilepsy, but their deployment is hampered by the blood-brain barrier (BBB). Previous studies showed that intracerebroventricular injection of an antisense oligonucleotide (antagomir) targeting microRNA-134 (Ant-134) reduced evoked and spontaneous seizures in animal models of epilepsy. In this study, we used assays of serum protein and tracer extravasation to determine that BBB disruption occurring after status epilepticus in mice was sufficient to permit passage of systemically injected Ant-134 into the brain parenchyma. Intraperitoneal and intravenous injection of Ant-134 reached the hippocampus and blocked seizure-induced upregulation of miR-134. A single intraperitoneal injection of Ant-134 at 2 h after status epilepticus in mice resulted in potent suppression of spontaneous recurrent seizures, reaching a 99.5% reduction during recordings at 3 months. The duration of spontaneous seizures, when they occurred, was also reduced in Ant-134-treated mice. In vivo knockdown of LIM kinase-1 (Limk-1) increased seizure frequency in Ant-134-treated mice, implicating de-repression of Limk-1 in the antagomir mechanism. These studies indicate that systemic delivery of Ant-134 reaches the brain and produces long-lasting seizure-suppressive effects after systemic injection in mice when timed with BBB disruption and may be a clinically viable approach for this and other disease-modifying microRNA therapies.
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