ArticleBrain : a journal of neurology2018
A novel metabolism-based phenotypic drug discovery platform in zebrafish uncovers HDACs 1 and 3 as a potential combined anti-seizure drug target.
Article in Brain : a journal of neurology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT03894826 (A Phase 2 Clinical Trial Testing the Safety and Efficacy of Voronistat in Pediatric Patients With Drug Resistant Epilepsy), which is not on this map. Cited by 38 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.
A Phase 2 Clinical Trial Testing the Safety and Efficacy of Voronistat in Pediatric Patients With Drug Resistant Epilepsy
Who cites it
38 citing papers in PubMed, 66 citations in OpenAlex.
- A staged zebrafish-mouse screening strategy for antiseizure compound prioritization.Neuropharmacology · 2026Article
- Review
- Chidamide Is Screened to Suppress Epileptogenesis in Mice Models via Blocking Histone Deacetylase 1.CNS neuroscience & therapeutics · 2026Article
- Automated detection of complex zebrafish seizure behavior at scale.Communications biology · 2025Article
- Modulation of NMDA receptor signaling and zinc chelation prevent seizure-like events in a zebrafish model of SLC13A5 epilepsy.PLoS biology · 2025Article
- Metabolic aspects of genetic ion channel epilepsies.Journal of neurochemistry · 2024Review
- Testing of putative antiseizure medications in a preclinical Dravet syndrome zebrafish model.Brain communications · 2024Article
- Testing of putative antiseizure drugs in a preclinical Dravet syndrome zebrafish model.bioRxiv : the preprint server for biology · 2023Article
- Suberoylanilide Hydroxamic Acid (SAHA) Is a Driver Molecule of Neuroplasticity: Implication for Neurological Diseases.Biomolecules · 2023Review
- The Promising Epigenetic Regulators for Refractory Epilepsy: An Adventurous Road Ahead.Neuromolecular medicine · 2023Review
- Fish Models for Exploring Mitochondrial Dysfunction Affecting Neurodegenerative Disorders.International journal of molecular sciences · 2023Review
- Intermittent hypoxia: linkage between OSAS and epilepsy.Frontiers in pharmacology · 2023Review
- Article
- Aquatic Freshwater Vertebrate Models of Epilepsy Pathology: Past Discoveries and Future Directions for Therapeutic Discovery.International journal of molecular sciences · 2022Review
- The metabolic basis of epilepsy.Nature reviews. Neurology · 2022Review
- Post-Traumatic Epilepsy and Comorbidities: Advanced Models, Molecular Mechanisms, Biomarkers, and Novel Therapeutic Interventions.Pharmacological reviews · 2022Review
- 2022 Overview of Metabolic Epilepsies.Genes · 2022Review
- Article
- Lactylation, an emerging hallmark of metabolic reprogramming: Current progress and open challenges.Frontiers in cell and developmental biology · 2022Review
- Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
12 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Despite the development of newer anti-seizure medications over the past 50 years, 30-40% of patients with epilepsy remain refractory to treatment. One explanation for this lack of progress is that the current screening process is largely biased towards transmembrane channels and receptors, and ignores intracellular proteins and enzymes that might serve as efficacious molecular targets. Here, we report the development of a novel drug screening platform that harnesses the power of zebrafish genetics and combines it with in vivo bioenergetics screening assays to uncover therapeutic agents that improve mitochondrial health in diseased animals. By screening commercially available chemical libraries of approved drugs, for which the molecular targets and pathways are well characterized, we were able to reverse-identify the proteins targeted by efficacious compounds and confirm the physiological roles that they play by utilizing other pharmacological ligands. Indeed, using an 870-compound screen in kcna1-morpholino epileptic zebrafish larvae, we uncovered vorinostat (Zolinza™; suberanilohydroxamic acid, SAHA) as a potent anti-seizure agent. We further demonstrated that vorinostat decreased average daily seizures by ∼60% in epileptic Kcna1-null mice using video-EEG recordings. Given that vorinostat is a broad histone deacetylase (HDAC) inhibitor, we then delineated a specific subset of HDACs, namely HDACs 1 and 3, as potential drug targets for future screening. In summary, we have developed a novel phenotypic, metabolism-based experimental therapeutics platform that can be used to identify new molecular targets for future drug discovery in epilepsy.
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.