Antisense Oligonucleotide Reverses Leukodystrophy in Canavan Disease Mice
Vanessa L. Hull, Yan Wang, Travis Burns, Sheng Zhang, Sarah Sternbach, Jennifer McDonough, Fuzheng Guo, David Pleasure
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.
Topics & Concepts
LeukodystrophyAtaxiaCerebellar ataxiaSpinocerebellar ataxiaChemistryMolecular biologyInternal medicineEndocrinologyBiologyDiseaseMedicineNeuroscienceAdvanced MRI Techniques and ApplicationsRNA regulation and diseaseMitochondrial Function and Pathology