Antisense Oligonucleotide Reverses Leukodystrophy in Canavan Disease Mice
- 22 January 2020
- journal article
- research article
- Published by Wiley in Annals of Neurology
- Vol. 87 (3) , 480-485
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;87:480–485Keywords
Funding Information
- National Institutes of Health (R21NS096004, RO1NS094559)
- Shriners Hospitals for Children (85113‐NCA1B)
- Dana Foundation (none)
This publication has 21 references indexed in Scilit:
- N-Acetylaspartate Synthase Deficiency Corrects the Myelin Phenotype in a Canavan Disease Mouse Model But Does Not Affect Survival TimeJournal of Neuroscience, 2015
- Ablating N‐acetylaspartate prevents leukodystrophy in a Canavan disease modelAnnals of Neurology, 2015
- A Single Intravenous rAAV Injection as Late as P20 Achieves Efficacious and Sustained CNS Gene Therapy in Canavan MiceMolecular Therapy, 2013
- Decreased NAA in Gray Matter is Correlated with Decreased Availability of Acetate in White Matter in Postmortem Multiple Sclerosis CortexNeurochemical Research, 2013
- Canavan disease, a rare early-onset human spongiform leukodystrophy: Insights into its genesis and possible clinical interventionsBiochimie, 2013
- Aspartoacylase-LacZ Knockin Mice: An Engineered Model of Canavan DiseasePLOS ONE, 2011
- Molecular identification of aspartate N-acetyltransferase and its mutation in hypoacetylaspartiaBiochemical Journal, 2009
- Nur7Is a Nonsense Mutation in the Mouse Aspartoacylase Gene That Causes Spongy Degeneration of the CNSThe Journal of Neuroscience, 2008
- Canavan disease: From spongy degeneration to molecular analysisThe Journal of Pediatrics, 1995
- Spongy degeneration of the central nervous system (Van Bogaert and Bertrand type; Canavan's disease)A reviewHuman Pathology, 1973