ArticleEMBO reports2024
Gene therapy for epilepsy targeting neuropeptide Y and its Y2 receptor to dentate gyrus granule cells.
Article in EMBO reports, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
What it found
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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
8 citing papers in PubMed.
- Epilepsy: Molecular Pathogenesis and Emerging Therapies.MedComm · 2026Review
- Gene therapy for epilepsy: An emerging, promising approach for a serious neurological disorder.Journal of internal medicine · 2026Review
- Apelin-13 confers Neuropeptide Y-mediated neuroprotection and preserves learning and allocentric memory in D-glutamic acid-induced excitotoxicity in rats.Molecular neurobiology · 2026Article
- Targeting Neuropeptide Y: Novel Approaches to the Treatment of Cardiovascular and Haematological Disorders.Cardiovascular & hematological disorders drug targets · 2026Review
- AAV-mediated gene therapy for focal epilepsy by expressing neuropeptide Y and Y2 receptor in rodent and non-human primate hippocampus.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Article
- Targeting the trunk of multi-root common epilepsy with gene therapy.Molecular therapy. Methods & clinical development · 2025Article
- Modulation of temporoammonic-CA1 synapses by neuropeptide Y is through Y1 receptors in mice.Neuropeptides · 2025Article
- Review
Corrections and comments
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Authors and funding
11 authors.
Funding
Abstract
Gene therapy is emerging as an alternative option for individuals with drug-resistant focal epilepsy. Here, we explore the potential of a novel gene therapy based on Neuropeptide Y (NPY), a well-known endogenous anticonvulsant. We develop a lentiviral vector co-expressing NPY with its inhibitory receptor Y2 in which, for the first time, both transgenes are placed under the control of the minimal CamKIIa(0.4) promoter, biasing expression toward excitatory neurons and allowing autoregulation of neuronal excitability by Y2 receptor-mediated inhibition. Vector-induced NPY and Y2 expression and safety are first assessed in cultures of hippocampal neurons. In vivo experiments demonstrate efficient and nearly selective overexpression of both genes in granule cell mossy fiber terminals following vector administration in the dentate gyrus. Telemetry video-EEG monitoring reveals a reduction in the frequency and duration of seizures in the synapsin triple KO model. This study shows that targeting a small subset of neurons (hippocampal granule cells) with a combined overexpression of NPY and Y2 receptor is sufficient to reduce the occurrence of spontaneous seizures.
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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.