ArticleHuman molecular genetics2021
Dimethyl fumarate dose-dependently increases mitochondrial gene expression and function in muscle and brain of Friedreich's ataxia model mice.
Article in Human molecular genetics, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers, 1 of them a synthesis that pooled it.
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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
17 citing papers in PubMed, 1 synthesis or guideline pooled it, 26 citations in OpenAlex.
- The Emerging Role of Dimethyl Fumarate in Alzheimer's Disease-A Systematic Review of Available Preclinical Studies.International journal of molecular sciences · 2026Pooled it
- Mitochondrial dynamics and repair differences in two mouse models of Friedreich's ataxia.The Journal of physiology · 2026Article
- Fumarate inhibits the formation of neutrophil extracellular traps (NETs) in a Nrf2-controlled and Annexin-A1-dependent manner associated with mitochondrial fusion.Frontiers in immunology · 2026Article
- Dimethyl fumarate and mitochondrial physiology: implications for neurological disorders.Frontiers in pharmacology · 2026Review
- Skeletal Muscle Pathology in Autosomal Recessive Cerebellar Ataxias: Insights from Marinesco-Sjögren Syndrome.International journal of molecular sciences · 2025Review
- Omaveloxolone, But Not Dimethyl Fumarate, Improves Cardiac Function in Friedreich's Ataxia Mice With Severe Cardiomyopathy.Journal of the American Heart Association · 2025Article
- Effect of dimethyl fumarate on mitochondrial metabolism in a pediatric porcine model of asphyxia-induced in-hospital cardiac arrest.Scientific reports · 2024Article
- Recent Advances in the Treatment Strategies of Friedreich's Ataxia: A Review of Potential Drug Candidates and their Underlying Mechanisms.Current pharmaceutical design · 2024Review
- Emerging antioxidant therapies in Friedreich's ataxia.Frontiers in pharmacology · 2024Review
- Targeting the NRF2 pathway for disease modification in neurodegenerative diseases: mechanisms and therapeutic implications.Frontiers in pharmacology · 2024Review
- Review
- Novel potential pharmacological applications of dimethyl fumarate-an overview and update.Frontiers in pharmacology · 2023Review
- Mitochondrial Impairments in Peripheral Blood Mononuclear Cells of Multiple Sclerosis Patients.Biology · 2022Article
- Dimethyl Fumarate Attenuates Pain Behaviors in Osteoarthritis Rats via Induction of Nrf2-Mediated Mitochondrial Biogenesis.Molecular pain · 2022Article
- Recessive cerebellar and afferent ataxias - clinical challenges and future directions.Nature reviews. Neurology · 2022Review
- A Drug Combination Rescues Frataxin-Dependent Neural and Cardiac Pathophysiology in FA Models.Frontiers in molecular biosciences · 2022Article
- Drug Repositioning in Friedreich Ataxia.Frontiers in neuroscience · 2022Review
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Previously we showed that dimethyl fumarate (DMF) dose-dependently increased mitochondrial gene expression and function in cells and might be considered as a therapeutic for inherited mitochondrial disease, including Friedreich's ataxia (FA). Here we tested DMF's ability to dose-dependently increase mitochondrial function, mitochondrial gene expression (frataxin and cytochrome oxidase protein) and mitochondrial copy number in C57BL6 wild-type mice and the FXNKD mouse model of FA. We first dosed DMF at 0-320 mg/kg in C57BL6 mice and observed significant toxicity above 160 mg/kg orally, defining the maximum tolerated dose. Oral dosing of C57BL6 mice in the range 0-160 mg/kg identified a maximum increase in aconitase activity and mitochondrial gene expression in brain and quadriceps at 110 mg/kg DMF, thus defining the maximum effective dose (MED). The MED of DMF in mice overlaps the currently approved human-equivalent doses of DMF prescribed for multiple sclerosis (480 mg/day) and psoriasis (720 mg/day). In the FXNKD mouse model of FA, which has a doxycycline-induced deficit of frataxin protein, we observed significant decreases of multiple mitochondrial parameters, including deficits in brain mitochondrial Complex 2, Complex 4 and aconitase activity, supporting the idea that frataxin deficiency reduces mitochondrial gene expression, mitochondrial functions and biogenesis. About 110 mg/kg of oral DMF rescued these enzyme activities in brain and rescued frataxin and cytochrome oxidase expression in brain, cerebellum and quadriceps muscle of the FXNKD mouse model. Taken together, these results support the idea of using fumarate-based molecules to treat FA or other mitochondrial diseases.
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Registered trials
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