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.
© 2020 American Neurological Association.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Acetyltransferases / antagonists & inhibitors
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Amidohydrolases / deficiency
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Amidohydrolases / genetics
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Animals
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Aspartic Acid / analogs & derivatives*
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Aspartic Acid / biosynthesis
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Ataxia / complications
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Ataxia / drug therapy
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Atrophy / complications
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Atrophy / drug therapy
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Canavan Disease / complications
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Canavan Disease / drug therapy*
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Canavan Disease / pathology
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Cerebellum / pathology
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Female
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Gene Knockdown Techniques
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Infusions, Intraventricular
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Male
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Mice
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Mutation
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Oligonucleotides, Antisense / administration & dosage
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Oligonucleotides, Antisense / therapeutic use*
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Purkinje Cells / pathology
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Rotarod Performance Test
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Thalamus / pathology
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Vacuoles / drug effects
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Vacuoles / pathology
Substances
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Oligonucleotides, Antisense
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Aspartic Acid
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N-acetylaspartate
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Acetyltransferases
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Shati protein, mouse
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Amidohydrolases
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aspartoacylase