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Huntington disease (HD) is a hereditary neurodegenerative disorder that affects movement, behavior, and cognition and leads to death within 20 years of disease onset. Cognitive impairment occurs early in the disease and deteriorates as HD progresses, contributing to loss of ability to work and perform activities of daily living. No effective treatments are currently available to alter the course of the disease or to improve cognition because tetrabenazine, the only approved therapy for HD, treats only chorea and other motor symptoms. Abnormal mitochondrial depolarization, which can lead to collapse of the mitochondrial membrane and ultimately neuronal apoptosis, has been implicated in the pathophysiologic progression of HD and other neurodegenerative diseases.1,2 Latrepirdine is a synthetic molecule that stabilizes mitochondrial membranes3,4 and increases neurite outgrowth to an extent comparable to the maximally effective dose of brain-derived neurotrophic factor in cultured neurons.4 Improvement in mitochondrial function may prevent apoptosis and also improve the efficiency of dynamic cellular activities, such as firing of action potentials and the maintenance or formation of synapses. Latrepirdine, 20 mg 3 times daily, has been studied in a randomized, double-blind, placebo-controlled trial in patients with mild to moderate Alzheimer disease (AD) and demonstrated significant improvement compared with placebo in cognitive, behavioral, and functional scores at 6 and 12 months.5 An earlier open-label, dose-escalation study in patients with HD suggested dosages up to 20 mg 3 times daily would be tolerated in this population.6 We studied the safety and tolerability of latrepirdine, 20 mg 3 times daily, and explored its effects on symptoms in patients with mild to moderate HD.