ArticleHuman molecular genetics2019
Pre-clinical evaluation of cysteamine bitartrate as a therapeutic agent for mitochondrial respiratory chain disease.
Article in Human molecular genetics, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 31 citations in OpenAlex.
- Systematic Engineering of Loss-of-Function Alleles in the Zebrafish Mitochondrial Proteome.bioRxiv : the preprint server for biology · 2026Article
- Mitochondrial DNA A3243G variant-associated MELAS: Recent advances in clinical trials, therapeutic interventions, and disease-modifying strategies.Intractable & rare diseases research · 2026Review
- Cystinosis and Cellular Energy Failure: Mitochondria at the Crossroads.International journal of molecular sciences · 2026Review
- Therapies for Mitochondrial Disease: Past, Present, and Future.Journal of inherited metabolic disease · 2025Review
- Article
- Polydatin and Nicotinamide Rescue the Cellular Phenotype of Mitochondrial Diseases by Mitochondrial Unfolded Protein Response (mtUPR) Activation.Biomolecules · 2024Article
- Flow cytometric analysis of hepatopancreatic cells from Armadillidium vulgare highlights terrestrial isopods as efficient environmental bioindicators in ex vivo settings.Environmental science and pollution research international · 2024Article
- Mitigative role of cysteamine against unilateral renal reperfusion injury in Wistar rats.Frontiers in pharmacology · 2024Article
- Functionalized and Nonfunctionalized Nanosystems for Mitochondrial Drug Delivery with Metallic Nanoparticles.Molecules (Basel, Switzerland) · 2023Review
- N-acetylcysteine and cysteamine bitartrate prevent azide-induced neuromuscular decompensation by restoring glutathione balance in two novel surf1-/- zebrafish deletion models of Leigh syndrome.Human molecular genetics · 2023Article
- Boosting Mitochondrial Potential: An Imperative Therapeutic Intervention in Amyotrophic Lateral Sclerosis.Current neuropharmacology · 2023Review
- Mitochondrion-targeted RNA therapies as a potential treatment strategy for mitochondrial diseases.Molecular therapy. Nucleic acids · 2022Review
- Dichloroacetate improves mitochondrial function, physiology, and morphology in FBXL4 disease models.JCI insight · 2022Article
- Cysteamine affects skeletal development and impairs motor behavior in zebrafish.Frontiers in pharmacology · 2022Article
- Combinatorial glucose, nicotinic acid and N-acetylcysteine therapy has synergistic effect in preclinical C. elegans and zebrafish models of mitochondrial complex I disease.Human molecular genetics · 2021Article
- Comparative Analysis of Experimental Methods to Quantify Animal Activity in Caenorhabditis elegans Models of Mitochondrial Disease.Journal of visualized experiments : JoVE · 2021Article
- The pursuit of precision mitochondrial medicine: Harnessing preclinical cellular and animal models to optimize mitochondrial disease therapeutic discovery.Journal of inherited metabolic disease · 2021Review
- Current and Emerging Clinical Treatment in Mitochondrial Disease.Molecular diagnosis & therapy · 2021Review
- Therapeutic Approaches to Treat Mitochondrial Diseases: "One-Size-Fits-All" and "Precision Medicine" Strategies.Pharmaceutics · 2020Review
- Mitochondrial Dynamics of Proximal Tubular Epithelial Cells in Nephropathic Cystinosis.International journal of molecular sciences · 2019Article
Corrections and comments
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Authors and funding
15 authors at 2 institutions in 1 country.
Funding
Abstract
Cysteamine bitartrate is a US Food and Drug Administration-approved therapy for nephropathic cystinosis also postulated to enhance glutathione biosynthesis. We hypothesized this antioxidant effect may reduce oxidative stress in primary mitochondrial respiratory chain (RC) disease, improving cellular viability and organismal health. Here, we systematically evaluated the therapeutic potential of cysteamine bitartrate in RC disease models spanning three evolutionarily distinct species. These pre-clinical studies demonstrated the narrow therapeutic window of cysteamine bitartrate, with toxicity at millimolar levels directly correlating with marked induction of hydrogen peroxide production. Micromolar range cysteamine bitartrate treatment in Caenorhabditis elegans gas-1(fc21) RC complex I (NDUFS2-/-) disease invertebrate worms significantly improved mitochondrial membrane potential and oxidative stress, with corresponding modest improvement in fecundity but not lifespan. At 10 to 100 μm concentrations, cysteamine bitartrate improved multiple RC complex disease FBXL4 human fibroblast survival, and protected both complex I (rotenone) and complex IV (azide) Danio rerio vertebrate zebrafish disease models from brain death. Mechanistic profiling of cysteamine bitartrate effects showed it increases aspartate levels and flux, without increasing total glutathione levels. Transcriptional normalization of broadly dysregulated intermediary metabolic, glutathione, cell defense, DNA, and immune pathways was greater in RC disease human cells than in C. elegans, with similar rescue in both models of downregulated ribosomal and proteasomal pathway expression. Overall, these data suggest cysteamine bitartrate may hold therapeutic potential in RC disease, although not through obvious modulation of total glutathione levels. Careful consideration is required to determine safe and effective cysteamine bitartrate concentrations to further evaluate in clinical trials of human subjects with primary mitochondrial RC disease.
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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.