ArticlePloS one2019
Targeting ferroptosis: A novel therapeutic strategy for the treatment of mitochondrial disease-related epilepsy.
Article in PloS one, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 55 papers, 1 of them a synthesis that pooled it.
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Who cites it
55 citing papers in PubMed, 1 synthesis or guideline pooled it, 98 citations in OpenAlex.
- Emerging perspectives on mitochondrial dysfunctioning and inflammation in epileptogenesis.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2021Pooled it
- The emerging role of trace elements in epilepsy and metabolic disorders: a new frontier in neurotherapeutics.Biometals : an international journal on the role of metal ions in biology, biochemistry, and medicine · 2026Review
- Long non-coding RNAs: Emerging regulators of diverse programmed cell death pathways in neurons.Neural regeneration research · 2026Article
- The Mechanism of Long Non-coding RNA GABPB1-AS1/SLC12A5 Regulating Neuronal Ferroptosis in Epileptic Seizures.Neurochemical research · 2026Article
- Molecular mechanisms of iron metabolism and ferroptosis in cardiovascular diseases and intervention strategies targeting natural products (Review).Molecular medicine reports · 2026Review
- Anti-Inflammatory and Antioxidant Strategies in Epilepsy: From Molecular Mechanisms to Threshold Management.International journal of molecular sciences · 2026Review
- Targeting the Gut-Brain-Ferroptosis Axis: Molecular Mechanisms and Therapeutic Potential in Alzheimer's Disease and Epilepsy.Journal of molecular neuroscience : MN · 2026Review
- Molecular mechanisms underlying the ferroptosis-induced epileptiform activity in mouse cortical slices.Frontiers in cellular neuroscience · 2026Article
- Advances in Cardiolipin Analysis: Applications in Central Nervous System Disorders and Nutrition Interventions.Biomolecules · 2026Review
- Ferroptosis and Alzheimer's disease: unraveling the molecular mechanisms and therapeutic opportunities.Frontiers in cell and developmental biology · 2026Review
- Mitochondria-Associated Endoplasmic Reticulum Membranes as Potential Therapeutic Targets in Epilepsy.CNS neuroscience & therapeutics · 2025Review
- Mitochondria-Mediated Mechanisms of Ferroptosis in Neurological Diseases.Neurochemical research · 2025Review
- Characterizing Population Pharmacokinetics of Vatiquinone in Healthy Volunteers and Patients with Friedreich's Ataxia.Pharmaceuticals (Basel, Switzerland) · 2025Article
- Therapies for Mitochondrial Disease: Past, Present, and Future.Journal of inherited metabolic disease · 2025Review
- Mitochondrial dysfunction in epilepsy: mechanistic insights and clinical strategies.Molecular biology reports · 2025Review
- The role of ACSL4 in stroke: mechanisms and potential therapeutic target.Molecular and cellular biochemistry · 2025Review
- The miR-34a-5p Promotes Hippocampal Neuronal Ferroptosis in Epilepsy by Regulating SIRT1.Neurochemical research · 2025Article
- Therapeutic Approach to Epilepsy in Patients with Mitochondrial Diseases.Yonsei medical journal · 2025Review
- Evaluating the efficacy of vatiquinone in preclinical models of Leigh syndrome and GPX4 deficiency.Orphanet journal of rare diseases · 2025Article
- Targeting Ferroptosis in Rare Neurological Disorders Including Pediatric Conditions: Innovations and Therapeutic Challenges.Biomedicines · 2025Review
Corrections and comments
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Authors and funding
29 authors at 7 institutions in 2 countries.
Funding
Abstract
backgroundMitochondrial disease is a family of genetic disorders characterized by defects in the generation and regulation of energy. Epilepsy is a common symptom of mitochondrial disease, and in the vast majority of cases, refractory to commonly used antiepileptic drugs. Ferroptosis is a recently-described form of iron- and lipid-dependent regulated cell death associated with glutathione depletion and production of lipid peroxides by lipoxygenase enzymes. Activation of the ferroptosis pathway has been implicated in a growing number of disorders, including epilepsy. Given that ferroptosis is regulated by balancing the activities of glutathione peroxidase-4 (GPX4) and 15-lipoxygenase (15-LO), targeting these enzymes may provide a rational therapeutic strategy to modulate seizure. The clinical-stage therapeutic vatiquinone (EPI-743, α-tocotrienol quinone) was reported to reduce seizure frequency and associated morbidity in children with the mitochondrial disorder pontocerebellar hypoplasia type 6. We sought to elucidate the molecular mechanism of EPI-743 and explore the potential of targeting 15-LO to treat additional mitochondrial disease-associated epilepsies.
methodsPrimary fibroblasts and B-lymphocytes derived from patients with mitochondrial disease-associated epilepsy were cultured under standardized conditions. Ferroptosis was induced by treatment with the irreversible GPX4 inhibitor RSL3 or a combination of pharmacological glutathione depletion and excess iron. EPI-743 was co-administered and endpoints, including cell viability and 15-LO-dependent lipid oxidation, were measured.
resultsEPI-743 potently prevented ferroptosis in patient cells representing five distinct pediatric disease syndromes with associated epilepsy. Cytoprotection was preceded by a dose-dependent decrease in general lipid oxidation and the specific 15-LO product 15-hydroxyeicosatetraenoic acid (15-HETE).
conclusionsThese findings support the continued clinical evaluation of EPI-743 as a therapeutic agent for PCH6 and other mitochondrial diseases with associated epilepsy.
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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.