Search

Abstract: Background: Mitochondrial DNA depletion syndromes are a group of heterogeneous autosomal recessive disorders associated with a severe reduction in mitochondrial DNA in the affected tissues. Sodium pyruvate has been reported to have a therapeutic effect in mitochondrial diseases. Methods: We analyzed the effects of 0.5g/kg of sodium pyruvate administered through a nasogastric tube in a one-year-old patient with myopathic mitochondrial DNA depletion syndrome. To evaluate the improvement, we used the Newcastle Paediatric Mitochondrial Disease Scale (NPMDS) and manual muscle testing. As the improvement of motor functions in this severely disabled infant could not be comprehensively detected by NPMDS, we also observed the infant''s ability to perform several tasks such as pouting, winking, and number of times she could tap a toy xylophone with a stick. Blood lactate and pyruvate levels were also monitored. Results: After one month''s treatment, the NPMDS score in section IV, the domain for the quality of life, improved from 17 to13. The infant became capable of raising her forearm, lower leg and wrist against gravity. The maximum number of times she could repeat each task increased and the movements became brisker and stronger. No significant change of the blood lactate level or lactate-to-pyruvate ratio, both of which were mildly increased at the initiation of the therapy, was observed despite the clinical improvement. Conclusion: Sodium pyruvate administered at 0.5g/kg improved the muscle strength and the NPMDS score of an infant with myopathic mitochondrial DNA depletion syndrome. General significance: Sodium pyruvate may be effective for ameliorating the clinical manifestations of mitochondrial diseases. This article is part of a Special Issue entitled: Biochemistry of Mitochondria. [Copyright &y& Elsevier]

Abstract: Background: Recently we proposed the therapeutic potential of pyruvate therapy for mitochondrial diseases. Leigh syndrome is a progressive neurodegenerative disorder ascribed to either mitochondrial or nuclear DNA mutations. Methods: In an attempt to circumvent the mitochondrial dysfunction, we orally applied sodium pyruvate and analyzed its effect on an 11-year-old female with Leigh syndrome due to cytochrome c oxidase deficiency accompanied by cardiomyopathy. The patient was administered sodium pyruvate at a maintenance dose of 0.5 g/kg/day and followed up for 1 year. Results: The exercise intolerance was remarkably improved so that she became capable of running. Echocardiography indicated improvements both in the left ventricle ejection fraction and in the fractional shortening. Electrocardiography demonstrated amelioration of the inverted T waves. When the pyruvate administration was interrupted because of a gastrointestinal infection, the serum lactate level became elevated and the serum pyruvate level, decreased, suggesting that the pyruvate administration was effective in decreasing the lactate-to-pyruvate ratio. Conclusions: These data indicate that pyruvate therapy was effective in improving exercise intolerance at least in a patient with cytochrome c oxidase deficiency. General significance: Administration of sodium pyruvate may prove effective for other patients with cytochrome c oxidase deficiency due to mitochondrial or nuclear DNA mutations. [Copyright &y& Elsevier]

Background: Mitochondrial disease is a term used to describe a set of heterogeneous genetic diseases caused by impaired structure or function of mitochondria. Pyruvate therapy for mitochondrial disease is promising from a clinical point of view., Methods: According to PRISMA guidelines, the following databases were searched to identify studies regarding pyruvate therapy for mitochondrial disease: PubMed, EMBASE, Cochrane Library, and Clinicaltrials . The search was up to April 2019. The endpoints were specific biomarkers (plasma level of lactate, plasma level of pyruvate, L/P ratio) and clinical rating scales [Japanese mitochondrial disease-rating scale (JMDRS), Newcastle Mitochondrial Disease Adult Scale (NMDAS), and others]. Two researchers independently screened articles, extracted data, and assessed the quality of the studies., Results: A total of six studies were included. Considerable differences were noted between studies in terms of study design, patient information, and outcome measures. The collected evidence may indicate an effective potential of pyruvate therapy on the improvement of mitochondrial disease. The majority of the common adverse events of pyruvate therapy were diarrhea and short irritation of the stomach., Conclusion: Pyruvate therapy with no serious adverse events may be a potential therapeutic candidate for patients with incurable mitochondrial diseases, such as Leigh syndrome. However, recent evidence taken from case series and case reports, and theoretical supports of basic research are not sufficient. The use of global registries to collect patient data and more adaptive trial designs with larger numbers of participants are necessary to clarify the efficacy of pyruvate therapy., Competing Interests: Conflict of interest statement: The authors declare that there is no conflict of interest., (© The Author(s), 2020.)