Dietary supplement a potential treatment for Canavan disease

New research indicates that a dietary supplement could be used as an effective treatment for Canavan disease (CD), which currently has no cure or standard of care. An article on the findings was published recently in the online Proceedings of the National Academy of Sciences.

CD is a relatively rare, but always fatal, inherited degenerative brain disease. A disorder of central nervous system (CNS), it affects myelin, the brain's white matter, which protects nerves and allows messages to be sent to and from the brain.

CD has been linked to mutations in the gene for the enzyme aspartoacylase (ASPA), which leads to the buildup of N-acetylaspartic acid (NAA) in the brain. Significant accumulation of NAA in the brain is closely associated with CD, which is characterized by the destruction of myelin. This causes the white matter to degenerate into spongy tissue riddled with microscopic fluid-filled spaces. However, the relation to accumulated NAA and the cause for the destruction of myelin is not known.

In this new research, myelin lipid synthesis was studied in the mouse model of Canavan disease. The objective was to test the hypothesis that deficiency in the supply of NAA-derived acetate results in decreased synthesis of myelin-related fatty acids and lipids, and that this lipid synthesis deficiency causes CD.

Analyses of newly synthesized lipids in the brain revealed significant decreases in four or five major myelin lipids in CD mice at the time of peak myelination. Acetate levels in the brain decreased by about 80% while acetate levels in the liver and kidney remained unchanged. Analysis of the lipid content of white matter from a human Canavan patient showed decreases in a number of myelin lipids relative to normal white matter.

These results demonstrate that myelin lipid synthesis is significantly compromised in CD, and provide the first direct evidence that defective myelin synthesis, resulting from a deficiency of NAA-de

Contact: Lisa Reilly
Henry M. Jackson Foundation for the Advancement of Military Medicine

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