DICHLOROACETATE IN MITOCHONDRIAL DISEASE

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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Dichloroacetate (DCA) appears to have some beneficial effect in patients with mitochondrial electron transport chain defects. This medication acts by stimulating the activity of the pyruvate dehydrogenase complex enzyme. The stimulation of this enzyme results in increased metabolism of pyruvate to acetyl CoA and away from lactate production. As such, it has been postulated that this medication would benefit patients with conditions such as mitochondrial cytopathies that result in elevated lactate levels. Although the clinical use of this medication has been limited, certain side effects have been identified. These have included an alteration of blood glucose metabolism such that hypoglycemia may result. Alterations in nerve conduction velocity have also been reported. The hypoglycemia effects of this drug appear to be more prominent in the initial phases of treatment and for this reason patients are monitored closely in the hospital setting with frequent blood glucose evaluations. it is also recommended that nerve conduction velocities be documented prior to the onset of this treatment and at regular intervals thereafter. The effect on nerve conduction is reportedly dose-related and a reduction in nerve conduction velocity would necessitate a decrease and possibly a cessation of this therapy. The patient will be followed at regular intervals with neurological examinations and nerve conduction studies.