Trial of dichloroacetate in MELAS

Mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes (MELAS) represents one of the most dramatic and widely recognized clinical presentations of mitochondrial disease. Typically the result of an A to G point mutation at nucleotide 3243 of the mitochondrial DNA (mtDNA),¹ patients present with headache, obtundation, encephalopathy, seizures, and stroke-like events. For many this will be their first presentation to a neurologic unit, events ranging in severity from transient visual field defects to fulminant cerebral infarction, status epilepticus, and death. Prevalence estimates for MELAS (and the mtDNA diseases as a whole) continue to increase as our clinical vigilance and diagnostic techniques improve.² Despite this, most neurologic centers see only small numbers, making adequately powered clinical trials difficult to initiate. The task is made harder by the notable lack of natural history data with which to draw comparison. Of paramount importance then is the need for well-designed clinical studies to guide the physician, so often misled by anecdotes.

In this issue of Neurology, Kaufmann et al.³ describe a double-blind, placebo-controlled, randomized, 3-year crossover trial of dichloroacetate (DCA) in 30 patients with MELAS and the 3243A>G mutation. The authors have previously reported a correlation between cerebral lactic acidosis and neurologic impairment in MELAS, yet any causal relationship remains unproven.⁴ The authors hypothesized that lowering lactate levels with DCA might limit neurologic decline, a view supported by open label DCA use in patients with MELAS.^5,6 However, …