ArticleGene therapy2014
Adenosine kinase, glutamine synthetase and EAAT2 as gene therapy targets for temporal lobe epilepsy.
Article in Gene therapy, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 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
23 citing papers in PubMed, 36 citations in OpenAlex.
- Advancing the Paradigm of Temporal Lobe Epilepsy as a Network Disease: The Promise of Biomarkers and Targeted Disease Modification.International journal of molecular sciences · 2026Review
- Targeted Gene and Genome-Editing Strategies for Epilepsy: Experimental Advances and Translational Challenges.International journal of molecular sciences · 2026Review
- Gene therapy for epilepsy: An emerging, promising approach for a serious neurological disorder.Journal of internal medicine · 2026Review
- Genetic medicines for epilepsy: unlocking new avenues for seizure control.Frontiers in bioengineering and biotechnology · 2026Review
- The interplay between metabolism and neuroinflammation in epilepsy: mechanisms and therapeutic perspectives.Journal of neuroinflammation · 2025Review
- Review
- Neuroprotective Efficacy and Complementary Treatment with Medicinal Herbs: A Comprehensive Review of Recent Therapeutic Approaches in Epilepsy Management.CNS & neurological disorders drug targets · 2025Review
- Adeno-Associated Viral Vectors in the Treatment of Epilepsy.International journal of molecular sciences · 2024Review
- Recent advances and current status of gene therapy for epilepsy.World journal of pediatrics : WJP · 2024Review
- Astrocyte-derived SerpinA3N promotes neuroinflammation and epileptic seizures by activating the NF-κB signaling pathway in mice with temporal lobe epilepsy.Journal of neuroinflammation · 2023Article
- Overview Article Astrocytes as Initiators of Epilepsy.Neurochemical research · 2023Review
- Comparative analysis of astrocytes in the prefrontal cortex of primates: Insights into the evolution of human brain energetics.The Journal of comparative neurology · 2022Article
- Gene and Cell Therapy for Epilepsy: A Mini Review.Frontiers in molecular neuroscience · 2022Review
- Prophylactic Activation of Shh Signaling Attenuates TBI-Induced Seizures in Zebrafish by Modulating Glutamate Excitotoxicity through Eaat2a.Biomedicines · 2021Article
- The role of astrocytic glutamate transporters GLT-1 and GLAST in neurological disorders: Potential targets for neurotherapeutics.Neuropharmacology · 2019Review
- Astrocyte-selective AAV gene therapy through the endogenous GFAP promoter results in robust transduction in the rat spinal cord following injury.Gene therapy · 2019Article
- Advances in the Potential Biomarkers of Epilepsy.Frontiers in neurology · 2019Review
- Bioinformatics Analysis of Microarray Profiling Identifies That the miR-203-3p Target Ppp2ca Aggravates Seizure Activity in Mice.Journal of molecular neuroscience : MN · 2018Article
- Destination Brain: the Past, Present, and Future of Therapeutic Gene Delivery.Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology · 2017Review
- Article
Corrections and comments
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Authors and funding
9 authors at 1 institution in 1 country.
Funding
Abstract
Astrocytes are an attractive cell target for gene therapy, but the validation of new therapeutic candidates is needed. We determined whether adeno-associated viral (AAV) vector-mediated overexpression of glutamine synthetase (GS) or excitatory amino-acid transporter 2 (EAAT2), or expression of microRNA targeting adenosine kinase (miR-ADK) in hippocampal astrocytes in the rat brain could modulate susceptibility to kainate-induced seizures and neuronal cell loss. Transgene expression was found predominantly in astrocytes following direct injection of glial-targeting AAV9 vectors by 3 weeks postinjection. ADK expression in miR-ADK vector-injected rats was reduced by 94-96% and was associated with an ~50% reduction in the duration of kainate-induced seizures and greater protection of dentate hilar neurons but not CA3 neurons compared with miR-control vector-injected rats. In contrast, infusion of AAV-GS and EAAT2 vectors did not afford any protection against seizures or neuronal damage as the level of transcriptional activity of the glial fibrillary acidic promoter was too low to drive any significant increase in transgenic GS or EAAT2 relative to the high endogenous levels of these proteins. Our findings support ADK as a prime therapeutic target for gene therapy of temporal lobe epilepsy and suggest that alternative approaches including the use of stronger glial promoters are needed to increase transgenic GS and EAAT2 expression to levels that may be required to affect seizure induction and propagation.
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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.