Lithium citrate for Canavan disease.

Current evidence suggests that the effects of lithium on metabolic and signaling pathways in the brain may vary depending on the specific clinical condition or disease model. For example, lithium increases levels of cerebral N-acetyl aspartate in patients with bipolar disorder but does not appear to affect N-acetyl aspartate levels in normal human subjects. Conversely, lithium significantly decreases whole-brain levels of N-acetyl aspartate in a rat genetic model of Canavan disease in which cerebral N-acetyl aspartate is chronically elevated. While N-acetyl aspartate is a commonly used surrogate marker for neuronal density and correlates with neuronal viability, grossly elevated whole-brain levels of N-acetyl aspartate in Canavan disease are associated with dysmyelination and mental retardation. This report describes the first clinical application of lithium in a human subject with Canavan disease. Spectroscopic and clinical changes were observed over the time period in which lithium was administered, which reversed during a 2-week wash-out period after withdrawal of lithium. This investigation reports decreased N-acetyl aspartate levels in the brain regions tested and magnetic resonance spectroscopic values that are more characteristic of normal development and myelination, suggesting that a larger, controlled trial of lithium may be warranted as supportive therapy for Canavan disease by decreasing abnormally elevated N-acetyl aspartate.