SHORT-TERM DICHLOROACETATE TREATMENT IMPROVES INDEXES OF CEREBRAL METABOLISM IN PATIENTS WITH MITOCHONDRIAL DISORDERS

We performed a short-term, double-blind, placebo-controlled, crossover trial of sodium dichloroacetate (DCA) therapy in 11 patients affected by various primary mitochondrial disorders. Independent measures of o xidative metabolism (venous blood metabolites, exercise testing, phosp horus magnetic resonance [MR] spectroscopy of muscle, and proton MR sp ectroscopy of brain) were used in order to monitor metabolic responses to the drug. One week of DCA treatment produced significant decreases (p < 0.05) in blood lactate, pyruvate, and alanine at rest and after bicycle exercise. Proton MR spectra collected from a supraventricular volume of interest in brain of seven of 11 patients also showed signif icant changes. Brain lactate/creatine ratio decreased by 42% during DC A treatment (p < 0.05). Brain choline/creatine ratio (which is low in patients with myelinopathies) increased by 18% (p < 0.01) after therap y. N-Acetylaspartate/creatine ratio (an index of neuronal damage or lo ss) increased by 8% after treatment (p < 0.05). Proton MR spectra coll ected in two of 11 patients from a volume of interest including the ba sal ganglia showed similar results (decrease of 36.6% in lactate/creat ine; increases of 16% in choline/creatine and 4.5% in N-acetylaspartat e/creatine). Phosphorus MR spectroscopy of muscle and self-assessed cl inical disability were unchanged. Our study indicates that short-term DCA treatment not only lowers blood lactate but also improves indices of both brain oxidative metabolism and neuronal and glial density or f unction.