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. Author manuscript; available in PMC: 2016 Jul 31.
Published in final edited form as: Nat Rev Neurol. 2013 Jul 2;9(8):474–481. doi: 10.1038/nrneurol.2013.129

Table 1.

Treatments evaluated in patients with mitochondrial diseases

Agent Specific mechanism(s) of action Highest level of clinical study in humans
Increase of substrate supply to respiratory chain
Carnitine Fatty acid transfer for citric acid cycle intermediates Case report71
Niacin Precursor for NADH, which transfers electrons from intermediates to the respiratory chain Case report72
Thiamine Enhancement of pyruvate dehydrogenase to decarboxylate pyruvate for oxidation Case report73
Dichloroacetate Inhibition of pyruvate dehydrogenase kinase to increase availability of pyruvate for oxidation Randomized, placebo-controlled crossover trial in MELAS due to m.3243A>G mutation (negative outcome)34
Augmentation of respiratory chain components
Riboflavin Precursor for flavin adenine dinucleotide, an electron carrier bound to complexes I and II Open-label study in complex I deficiency (positive outcome)8
Coenzyme Q10 Electron carrier from complexes I and II to complex III Randomized, placebo-controlled crossover trial (negative outcome)32
Idebenone Analogue of coenzyme Q10 Randomized, placebo-controlled trial in Leber hereditary optic neuropathy (negative outcome)36
EPI-743 Analogue of vitamin E Open-label study in Leigh syndrome and Leber hereditary optic neuropathy (positive outcome)39,47
Bypass of respiratory chain components
Succinate Citric acid cycle intermediate which donates electrons directly to complexes I and II, thus partially bypassing complex I Case report12
Vitamins C and K Bypass of complex III Case report13
Energy buffering
Creatine ATP storage in muscles via the creatine phosphokinase system Randomized, placebo-controlled crossover trials in mitochondrial myopathies (negative outcomes in two trials, positive surrogate end points in one trial)35,52,73
Antioxidant activity
Cysteine Increases muscle availability of glutathione peroxidase Randomized, placebo-controlled crossover trial in progressive external ophthalmoplegia (negative outcome)14
Lipoic acid β-ketoacid dehydrogenase cofactor with antioxidant properties Case report66; randomized, placebo-controlled crossover trial (with creatine and coenzyme Q10; negative outcomes in various mitochondrial myopathies)46
Dimethylglycine Antioxidant activity Randomized, placebo-controlled crossover trial in Saguenay Lac-St-Jean cytochrome c oxidase deficiency (negative outcome)15
Oxidative capacity adaptations
Aerobic exercise training Reversal of deconditioning and/or mitochondrial adaptation to improve oxidative capacity Randomized, non-blinded controlled trial in mitochondrial myopathies (positive outcome)17,51,65,75
Resistance exercise training Myofibre regeneration and presumed gene shifting Open-label study (positive outcome)76,77
Nitric oxide metabolism
Arginine Substrate for nitric oxide synthase Open-label placebo-controlled trial in MELAS due to m.3243A>G mutation (positive outcome)18

Abbreviation: MELAS, mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes.

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