Clinical and Molecular Genetical Research for the Treatment of Mitochondrial Encephalomyopathies

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Mitochondrial encephalomyopathy is caused by mitochondrial dysfunction mainly in electron transport system in the inner mitochondrial membrane. The essential treatment has not yet been established, partly because the clinical effect of the treatment has been well evaluated from the point of the serial changes of mitochondrial enzyme activity and mitochondrial (mt) DNA analyses. We developed the methods of mitochondrial enzyme activities and mtDNA analyses in platelet (PLT). We also developed creatine monohydrate (Cr-H_2O) treatment for the mitochondrial encephalomyopathies.Miniaturized assays for isolated PLT were employed for the measurement of protein, complex II+III (II+III), complex IV (IV), and citrate synthase (CS) assays using a microplate reader. We newly developed the miniaturized assay for (IV). A3243G mutation of mtDNA was analyzed with PCR/RFLP methtod for the isolated PLT.We evaluated the stroke-like episode in a patient with MELAS and the efficacy of sodium dichloroacetat … More e (DCA) treatment using PLT mitochondrial enzyme assay. Although her muscle weakness improved with cytochrome c treatment, neurological symptoms including headache, vomiting and visual disturbance developed to intractable headache, which was a mild form of stroke-like episode. The intractable severe headache improved with DCA treatment. PLT (II+III), (IV) and (IV/CS) decreased at the stroke-like episode and DCA treatment improved PLT (II+III), (IV), and (IV/CS). Ratio of A3243G mutation of mtDNA was not changed before and after DCA treatment.Cr-H_2O was orally supplemented (0.2 g/kg/day, divided into two for the first two weeks followed by 0.08-0.12 g/kg/day twice or three times a day for 4-10 months) in two girls with MELAS due to an nt A3243G mtDNA mutation. The brain function was evaluated with frequency analysis of EEG and ^1H MRS.the results demonstrated that Cr-H_2O supplement improved the brain function of MELAS, suggesting the possibility of Cr-H_2O treatment for mitochondrial encephalomyopathy. Less