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

中文翻译：

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反义寡核苷酸逆转 Canavan 病小鼠的脑白质营养不良

N-乙酰-L-天冬氨酸 (NAA) 脑浓度的显着升高是 Canavan 病的一个特征，这是一种由少突胶质细胞 NAA 裂解酶天冬氨酸酰化酶缺乏引起的空泡性脑白质营养不良。我们现在证明，通过向年轻成年天冬氨酸酰化酶缺陷小鼠脑池内施用锁核酸反义寡核苷酸来抑制 NAA 合成，可以逆转它们先前存在的共济失调，并减少小脑和丘脑空泡形成以及浦肯野细胞树突状萎缩。Ann Neurol 2020；87：480–485