Lithium Citrate for Canavan Disease

Janson, Christopher G.; Assadi, Mitra; Francis, Jeremy; Bilaniuk, Larissa; Shera, David; Leone, Paola

doi:10.1016/j.pediatrneurol.2005.04.015

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Volume 33, Issue 4 , Pages 235-243, October 2005

Lithium Citrate for Canavan Disease

Christopher G. Janson, MD
- Department of Neurosurgery and Molecular Genetics, University of Medicine and Dentistry of New Jersey-Robert Wood Johnson Medical School, Camden, New Jersey
- Department of Neurology, University of Medicine and Dentistry of New Jersey-Robert Wood Johnson Medical School, Camden, New Jersey
- Division of Neuroradiology, University of Pennsylvania Medical Center and Children’s Hospital of Philadelphia, Philadelphia, Pennsylvania
- Communications should be addressed to: Dr. Janson; The Cell and Gene Therapy Center; 401 Haddon Avenue, Suite #388; Camden, NJ 08103.
Mitra Assadi, MD
- Department of Neurology, University of Medicine and Dentistry of New Jersey-Robert Wood Johnson Medical School, Camden, New Jersey
Jeremy Francis, PhD
- Department of Neurosurgery and Molecular Genetics, University of Medicine and Dentistry of New Jersey-Robert Wood Johnson Medical School, Camden, New Jersey
Larissa Bilaniuk, MD
- Division of Neuroradiology, University of Pennsylvania Medical Center and Children’s Hospital of Philadelphia, Philadelphia, Pennsylvania
David Shera, ScD
- Department of Biostatistics, University of Pennsylvania Medical Center and Children’s Hospital of Philadelphia, Philadelphia, Pennsylvania
Paola Leone, PhD
- Department of Neurosurgery and Molecular Genetics, University of Medicine and Dentistry of New Jersey-Robert Wood Johnson Medical School, Camden, New Jersey
- Division of Neuroradiology, University of Pennsylvania Medical Center and Children’s Hospital of Philadelphia, Philadelphia, Pennsylvania

Received 26 January 2005; accepted 4 April 2005.

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.