ArticleEBioMedicine2019
Rapamycin administration is not a valid therapeutic strategy for every case of mitochondrial disease.
Article in EBioMedicine, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 56 citations in OpenAlex.
- Comparative analysis of muscle pathologies and metabolic signaling in mouse models of mitochondrial dysfunction.Scientific reports · 2026Article
- Activation of the protective arm of renin-angiotensin system enhances mitochondrial turnover improving respiration and decreasing integrated stress response in a human Complex III deficiency model.bioRxiv : the preprint server for biology · 2026Article
- N-Acetylglucosamine Selectively Attenuates Neuroinflammation in a Mouse Model of Mitochondrial Dysfunction.Acta physiologica (Oxford, England) · 2026Article
- Biological and translational attributes of mitochondrial DNA copy number: Laboratory perspective to clinical relevance.World journal of methodology · 2025Review
- Preclinical evaluation of candidate "kill or cure" strategies to treat MFN2-related lipodystrophy.Molecular medicine (Cambridge, Mass.) · 2025Article
- The treatment of primary CoQ deficiency requires the targeting of multiple pathogenic mechanisms.Communications medicine · 2025Article
- The Balance of MFN2 and OPA1 in Mitochondrial Dynamics, Cellular Homeostasis, and Disease.Biomolecules · 2025Review
- Interactions of mitochondrial and skeletal muscle biology in mitochondrial myopathy.The Biochemical journal · 2023Review
- Neurological Phenotypes in Mouse Models of Mitochondrial Disease and Relevance to Human Neuropathology.International journal of molecular sciences · 2023Review
- Peripheral tissular analysis of rapamycin's effect as a neuroprotective agent in vivo.Naunyn-Schmiedeberg's archives of pharmacology · 2022Article
- Genomic signature of MTOR could be an immunogenicity marker in human colorectal cancer.BMC cancer · 2022Article
- Constitutive activation of the PI3K-Akt-mTORC1 pathway sustains the m.3243 A > G mtDNA mutation.Nature communications · 2021Article
- Animal Models of Coenzyme Q Deficiency: Mechanistic and Translational Learnings.Antioxidants (Basel, Switzerland) · 2021Review
- β-RA Targets Mitochondrial Metabolism and Adipogenesis, Leading to Therapeutic Benefits against CoQ Deficiency and Age-Related Overweight.Biomedicines · 2021Article
- Minimal mitochondrial respiration is required to prevent cell death by inhibition of mTOR signaling in CoQ-deficient cells.Cell death discovery · 2021Article
- Mitochondrial DNA copy number in human disease: the more the better?FEBS letters · 2021Review
- Moving towards clinical trials for mitochondrial diseases.Journal of inherited metabolic disease · 2021Review
- Therapeutic Approaches to Treat Mitochondrial Diseases: "One-Size-Fits-All" and "Precision Medicine" Strategies.Pharmaceutics · 2020Review
- Mitochondrial spongiotic brain disease: astrocytic stress and harmful rapamycin and ketosis effect.Life science alliance · 2020Article
- Bioenergetics and translational metabolism: implications for genetics, physiology and precision medicine.Biological chemistry · 2019Review
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Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
Abstract
backgroundThe vast majority of mitochondrial disorders have limited the clinical management to palliative care. Rapamycin has emerged as a potential therapeutic drug for mitochondrial diseases since it has shown therapeutic benefits in a few mouse models of mitochondrial disorders. However, the underlying therapeutic mechanism is unclear, the minimal effective dose needs to be defined and whether this therapy can be generally used is unknown.
methodsWe have evaluated whether low and high doses of rapamycin administration may result in therapeutic effects in a mouse model (Coq9
findingsLow dose of rapamycin induces metabolic changes in liver and transcriptomics modifications in midbrain. The high dose of rapamycin induces further changes in the transcriptomics profile in midbrain due to the general inhibition of mTORC1. However, neither low nor high dose of rapamycin were able to improve the mitochondrial bioenergetics, the brain injuries and the phenotypic characteristics of Coq9
interpretationThese results may be due to the lack of microgliosis-derived neuroinflammation, the limitation to induce autophagy, or the need of a functional CoQ-junction. Therefore, the translation of rapamycin therapy into the clinic for patients with mitochondrial disorders requires, at least, the consideration of the particularities of each mitochondrial disease. FUND: Supported by the grants from "Fundación Isabel Gemio - Federación Española de Enfermedades Neuromusculares - Federación FEDER" (TSR-1), the NIH (P01HD080642) and the ERC (Stg-337327).
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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.