ArticleNature medicine2014
Prevention and reversal of severe mitochondrial cardiomyopathy by gene therapy in a mouse model of Friedreich's ataxia.
Article in Nature medicine, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 136 papers, 1 of them a synthesis that pooled it.
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Who cites it
136 citing papers in PubMed, 1 synthesis or guideline pooled it, 227 citations in OpenAlex.
- Pharmacological treatments for Friedreich ataxia.The Cochrane database of systematic reviews · 2016Pooled it
- Serial assessment of echocardiographic measures in Friedreich ataxia.American heart journal plus : cardiology research and practice · 2026Article
- Mitochondrial Quality Control in Inherited Mitochondrial Cardiomyopathy: Convergent Pathobiology and a Testable Therapeutic Framework.International journal of molecular sciences · 2026Review
- Advances in Gene and Cellular Therapy in Friedreich Ataxia.Molecular diagnosis & therapy · 2026Review
- Adeno-Associated virus-based approaches for mitochondrial diseases: advances and challenges.Molecular psychiatry · 2026Review
- Myeloid cell replacement induces intercellular mitochondrial transfer and restores metabolism in a mouse model of mitochondrial disease.Nature communications · 2026Article
- Hepatic gene replacement improves energy metabolism and survival in a mouse model of neonatal mitochondrial disease GRACILE syndrome.Molecular therapy : the journal of the American Society of Gene Therapy · 2026Article
- AAVrh.10hFXN Gene Therapy for the Cardiomyopathy of Friedreich Ataxia: A Nonrandomized Clinical Trial.JAMA cardiology · 2026Article
- Development of a secretable frataxin for enhanced efficacy in treating Friedreich's Ataxia.Molecular therapy. Advances · 2026Article
- Development of an AAV-based gene therapy for the ocular phenotype of Friedreich's ataxia.Molecular therapy : the journal of the American Society of Gene Therapy · 2026Article
- Cerebellar deep brain stimulation rescues Purkinje cell mitochondrial density in a genetic mouse model of cerebellar ataxia.Brain research bulletin · 2026Article
- Peripheral frataxin levels govern long-term clinical progression in Friedreich ataxia.BMJ neurology open · 2026Article
- Recent developments in Friedreich's ataxia: a state-of-the-art review.Brain communications · 2026Review
- Systematic Phenotyping and Molecular Analysis of the Woozy Mouse: A Preclinical Model of Cerebellar Ataxia.Molecular neurobiology · 2025Article
- Alpha-lipoic acid supplementation improves pathological alterations in cellular models of Friedreich ataxia.Orphanet journal of rare diseases · 2025Article
- Inhibition of Rho-Associated Kinases ROCK1 and ROCK2 as a Therapeutic Strategy to Reactivate the RepressedThe Journal of neuroscience : the official journal of the Society for Neuroscience · 2025Article
- Pharmacokinetics and Pharmacodynamics of Nomlabofusp in Non-clinical Studies of Friedreich's Ataxia.The AAPS journal · 2025Article
- Gene therapy prevents onset of mitochondrial cardiomyopathy in neonatal mice with Ndufs6 deficiency.Cell death discovery · 2025Article
- A global perspective on research advances and future challenges in Friedreich ataxia.Nature reviews. Neurology · 2025Review
- Engineered mitochondria in diseases: mechanisms, strategies, and applications.Signal transduction and targeted therapy · 2025Review
76 more citing papers are in PubMed but not listed here.
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Authors and funding
9 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Cardiac failure is the most common cause of mortality in Friedreich's ataxia (FRDA), a mitochondrial disease characterized by neurodegeneration, hypertrophic cardiomyopathy and diabetes. FRDA is caused by reduced levels of frataxin (FXN), an essential mitochondrial protein involved in the biosynthesis of iron-sulfur (Fe-S) clusters. Impaired mitochondrial oxidative phosphorylation, bioenergetics imbalance, deficit of Fe-S cluster enzymes and mitochondrial iron overload occur in the myocardium of individuals with FRDA. No treatment exists as yet for FRDA cardiomyopathy. A conditional mouse model with complete frataxin deletion in cardiac and skeletal muscle (Mck-Cre-Fxn(L3/L-) mice) recapitulates most features of FRDA cardiomyopathy, albeit with a more rapid and severe course. Here we show that adeno-associated virus rh10 vector expressing human FXN injected intravenously in these mice fully prevented the onset of cardiac disease. Moreover, later administration of the frataxin-expressing vector, after the onset of heart failure, was able to completely reverse the cardiomyopathy of these mice at the functional, cellular and molecular levels within a few days. Our results demonstrate that cardiomyocytes with severe energy failure and ultrastructure disorganization can be rapidly rescued and remodeled by gene therapy and establish the preclinical proof of concept for the potential of gene therapy in treating FRDA cardiomyopathy.
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