ArticleScience translational medicine2013
Phenylbutyrate therapy for pyruvate dehydrogenase complex deficiency and lactic acidosis.
Article in Science translational medicine, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 3 registered trials, which are not on this map. Cited by 41 papers, 1 of them a synthesis that pooled it.
What it found
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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.
Phase 3 Trial of Dichloroacetate in Pyruvate Dehydrogenase Complex Deficiency:
Pilot Clinical Trial to Investigate the Safety and Efficacy of Phenylbutyrate Therapy for Patients With Pyruvate Dehydrogenase Complex Deficiency.
A Phase II, Multicentric, Prospective, Non-comparative Clinical Trial to Assess the Efficacy and Safety of the Treatment of Pyruvate Dehydrogenase Deficiency (PDH) Patients With Glycerol Phenybutyrate (RAVICTI®)
Who cites it
41 citing papers in PubMed, 1 synthesis or guideline pooled it, 70 citations in OpenAlex.
- Evaluation of Metabolic and Synaptic Dysfunction Hypotheses of Alzheimer's Disease (AD): A Meta-Analysis of CSF Markers.Current Alzheimer research · 2018Pooled it
- The genotypic and phenotypic landscape of PDHA1-related pyruvate dehydrogenase complex deficiency.Brain : a journal of neurology · 2026Article
- Animal models of pyruvate dehydrogenase complex deficiency: insight into mechanisms of cerebral abnormalities and tissue-specific role in metabolism.Frontiers in medicine · 2026Review
- Carcinogenesis: An Alternative Hypothesis Comparing Mutagenic Versus Metabolic Models.Biology · 2025Review
- Therapies for Mitochondrial Disease: Past, Present, and Future.Journal of inherited metabolic disease · 2025Review
- Type 3 diabetes and metabolic reprogramming of brain neurons: causes and therapeutic strategies.Molecular medicine (Cambridge, Mass.) · 2025Review
- Sodium Phenylbutyrate Attenuates Cisplatin-Induced Acute Kidney Injury Through Inhibition of Pyruvate Dehydrogenase Kinase 4.Biomedicines · 2024Article
- Vitamin-C-dependent downregulation of the citrate metabolism pathway potentiates pancreatic ductal adenocarcinoma growth arrest.Molecular oncology · 2024Article
- Phenylbutyrate and Dichloroacetate Enhance the Liquid-Stored Boar Sperm Quality via PDK1 and PDK3.International journal of molecular sciences · 2023Article
- Comparison Between Dichloroacetate and Phenylbutyrate Treatment for Pyruvate Dehydrogenase Deficiency.British journal of biomedical science · 2022Review
- PKAN hiPS-Derived Astrocytes Show Impairment of Endosomal Trafficking: A Potential Mechanism Underlying Iron Accumulation.Frontiers in cellular neuroscience · 2022Article
- Clinical Experience of Neurological Mitochondrial Diseases in Children and Adults: A Single-Center Study.Balkan journal of medical genetics : BJMG · 2021Article
- Genetic Testing in Various Neurodevelopmental Disorders Which Manifest as Cerebral Palsy: A Case Study From Iran.Frontiers in pediatrics · 2021Article
- Article
- A Great Catch for Investigating Inborn Errors of Metabolism-Insights Obtained from Zebrafish.Biomolecules · 2020Review
- The changing landscape of clinical trials for mitochondrial diseases: 2011 to present.Mitochondrion · 2020Review
- Fishing in the Cell Powerhouse: Zebrafish as A Tool for Exploration of Mitochondrial Defects Affecting the Nervous System.International journal of molecular sciences · 2019Review
- Pyruvate dehydrogenase complex deficiency is linked to regulatory loop disorder in the αV138M variant of human pyruvate dehydrogenase.The Journal of biological chemistry · 2018Article
- Folding and assembly defects of pyruvate dehydrogenase deficiency-related variants in the E1α subunit of the pyruvate dehydrogenase complex.Cellular and molecular life sciences : CMLS · 2018Article
- Pyruvate dehydrogenase complex and lactate dehydrogenase are targets for therapy of acute liver failure.Journal of hepatology · 2018Article
Corrections and comments
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Authors and funding
10 authors at 4 institutions in 2 countries.
Funding
Abstract
Lactic acidosis is a buildup of lactic acid in the blood and tissues, which can be due to several inborn errors of metabolism as well as nongenetic conditions. Deficiency of pyruvate dehydrogenase complex (PDHC) is the most common genetic disorder leading to lactic acidosis. Phosphorylation of specific serine residues of the E1α subunit of PDHC by pyruvate dehydrogenase kinase (PDK) inactivates the enzyme, whereas dephosphorylation restores PDHC activity. We found that phenylbutyrate enhances PDHC enzymatic activity in vitro and in vivo by increasing the proportion of unphosphorylated enzyme through inhibition of PDK. Phenylbutyrate given to C57BL/6 wild-type mice results in a significant increase in PDHC enzyme activity and a reduction of phosphorylated E1α in brain, muscle, and liver compared to saline-treated mice. By means of recombinant enzymes, we showed that phenylbutyrate prevents phosphorylation of E1α through binding and inhibition of PDK, providing a molecular explanation for the effect of phenylbutyrate on PDHC activity. Phenylbutyrate increases PDHC activity in fibroblasts from PDHC-deficient patients harboring various molecular defects and corrects the morphological, locomotor, and biochemical abnormalities in the noa(m631) zebrafish model of PDHC deficiency. In mice, phenylbutyrate prevents systemic lactic acidosis induced by partial hepatectomy. Because phenylbutyrate is already approved for human use in other diseases, the findings of this study have the potential to be rapidly translated for treatment of patients with PDHC deficiency and other forms of primary and secondary lactic acidosis.
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What OpenQuestion holds
Registered trials
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.