Antisense Oligonucleotide Reverses Leukodystrophy in Canavan Disease Mice.

Abstract

Marked elevation in the brain concentration of N-acetyl-L-aspartate (NAA) is a characteristic feature of Canavan disease, a vacuolar leukodystrophy resulting from deficiency of the oligodendroglial NAA-cleaving enzyme aspartoacylase. We now demonstrate that inhibiting NAA synthesis by intracisternal administration of a locked nucleic acid antisense oligonucleotide to young-adult aspartoacylase-deficient mice reverses their pre-existing ataxia and diminishes cerebellar and thalamic vacuolation and Purkinje cell dendritic atrophy. Ann Neurol 2020;87:480-485.

• Authors: Vanessa Hull, Yan Wang, Travis Burns, Sheng Zhang, Sarah Sternbach, Jennifer McDonough, Fuzheng Guo, David Pleasure
• Journal: Annals of neurology (Ann Neurol) Vol. 87 Issue 3 Pg. 480-485 (03 2020) ISSN: 1531-8249 [Electronic] United States
• PMID: 31925837 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: © 2020 American Neurological Association.

Chemical References

• Oligonucleotides, Antisense
• Aspartic Acid
• N-acetylaspartate
• Acetyltransferases
• Shati protein, mouse
• Amidohydrolases
• aspartoacylase

Topics

• Acetyltransferases (antagonists & inhibitors)
• Amidohydrolases (deficiency, genetics)
• Animals
• Aspartic Acid (analogs & derivatives, biosynthesis)
• Ataxia (complications, drug therapy)
• Atrophy (complications, drug therapy)
• Canavan Disease (complications, drug therapy, pathology)
• Cerebellum (pathology)
• Female
• Gene Knockdown Techniques
• Infusions, Intraventricular
• Male
• Mice
• Mutation
• Oligonucleotides, Antisense (administration & dosage, therapeutic use)
• Purkinje Cells (pathology)
• Rotarod Performance Test
• Thalamus (pathology)
• Vacuoles (drug effects, pathology)