Antisense Oligonucleotide Reverses Leukodystrophy in Canavan Disease Mice.

Hull, Vanessa; Wang, Yan; Burns, Travis; Zhang, Sheng; Sternbach, Sarah; McDonough, Jennifer; Guo, Fuzheng; Pleasure, David · Ann Neurol · 2020

basic_science · Level V

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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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