ArticleHuman molecular genetics2023
Skeletal muscle transcriptomics dissects the pathogenesis of Friedreich's ataxia.
Article in Human molecular genetics, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
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Who cites it
8 citing papers in PubMed, 7 citations in OpenAlex.
- Neuropathology of Friedreich ataxia and its links to metabolic pathways.Neurodegenerative disease management · 2026Review
- Myeloid cell replacement induces intercellular mitochondrial transfer and restores metabolism in a mouse model of mitochondrial disease.Nature communications · 2026Article
- Mitochondrial control of amino acid catabolism by a fasting-inducible mitochondrial carrier.Science advances · 2026Article
- Friedreich ataxia transcriptomic dysregulation and identification of cell type-specific biomarkers: A systematic review and meta-analysis.bioRxiv : the preprint server for biology · 2026Article
- A global perspective on research advances and future challenges in Friedreich ataxia.Nature reviews. Neurology · 2025Review
- Differential Gene Expression in Late-Onset Friedreich Ataxia: A Comparative Transcriptomic Analysis Between Symptomatic and Asymptomatic Sisters.International journal of molecular sciences · 2024Article
- Skeletal Muscle Involvement in Friedreich Ataxia.International journal of molecular sciences · 2024Review
- Skeletal muscle proteome analysis underpins multifaceted mitochondrial dysfunction in Friedreich's ataxia.Frontiers in neuroscience · 2023Article
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Authors and funding
13 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
objectiveIn Friedreich's ataxia (FRDA), the most affected tissues are not accessible to sampling and available transcriptomic findings originate from blood-derived cells and animal models. Herein, we aimed at dissecting for the first time the pathophysiology of FRDA by means of RNA-sequencing in an affected tissue sampled in vivo.
methodsSkeletal muscle biopsies were collected from seven FRDA patients before and after treatment with recombinant human Erythropoietin (rhuEPO) within a clinical trial. Total RNA extraction, 3'-mRNA library preparation and sequencing were performed according to standard procedures. We tested for differential gene expression with DESeq2 and performed gene set enrichment analysis with respect to control subjects.
resultsFRDA transcriptomes showed 1873 genes differentially expressed from controls. Two main signatures emerged: (1) a global downregulation of the mitochondrial transcriptome as well as of ribosome/translational machinery and (2) an upregulation of genes related to transcription and chromatin regulation, especially of repressor terms. Downregulation of the mitochondrial transcriptome was more profound than previously shown in other cellular systems. Furthermore, we observed in FRDA patients a marked upregulation of leptin, the master regulator of energy homeostasis. RhuEPO treatment further enhanced leptin expression.
interpretationOur findings reflect a double hit in the pathophysiology of FRDA: a transcriptional/translational issue and a profound mitochondrial failure downstream. Leptin upregulation in the skeletal muscle in FRDA may represent a compensatory mechanism of mitochondrial dysfunction, which is amenable to pharmacological boosting. Skeletal muscle transcriptomics is a valuable biomarker to monitor therapeutic interventions in FRDA.
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