Antisense Oligonucleotide Reverses Leukodystrophy in Canavan Disease Mice. Issue 3 (22nd January 2020)

• Record Type: Journal Article
• Authors: Hull, Vanessa; Wang, Yan; Burns, Travis; Zhang, Sheng; Sternbach, Sarah; McDonough, Jennifer; Guo, Fuzheng; Pleasure, David
• Is Part Of: Annals of neurology. Volume 87:Issue 3(2020)
• Page Start: 480
• Page End: 485
• Publication Date: 2020-01-22
• Subjects: Neurology -- Periodicals; Pediatric neurology -- Periodicals; Nervous system -- Surgery -- Periodicals; 616.8
• DOI: 10.1002/ana.25674
• Languages: English
• ISSNs: 0364-5134

Abstract

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