Antisense Oligonucleotide Reverses Leukodystrophy in Canavan Disease Mice

Vanessa Hull; Yan Wang; Travis Burns; Sheng Zhang; Sarah Sternbach; Jennifer McDonough; Fuzheng Guo; David Pleasure

doi:10.1002/ana.25674

Antisense Oligonucleotide Reverses Leukodystrophy in Canavan Disease Mice

Vanessa Hull, Yan Wang, Travis Burns, Sheng Zhang, Sarah Sternbach, Jennifer McDonough, Fuzheng Guo, David Pleasure

Neurology

Research output: Contribution to journal › Article › peer-review

7 Scopus citations

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.

Original language	English (US)
Pages (from-to)	480-485
Number of pages	6
Journal	Annals of Neurology
Volume	87
Issue number	3
DOIs	https://doi.org/10.1002/ana.25674
State	Published - Mar 1 2020

ASJC Scopus subject areas

Neurology
Clinical Neurology

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10.1002/ana.25674

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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.",

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AU - Hull, Vanessa

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AU - Zhang, Sheng

AU - Sternbach, Sarah

AU - McDonough, Jennifer

AU - Guo, Fuzheng

AU - Pleasure, David

PY - 2020/3/1

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N2 - 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.

AB - 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.

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Antisense Oligonucleotide Reverses Leukodystrophy in Canavan Disease Mice

Abstract

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