The pathogenesis of, and pharmacological treatment for, Canavan disease

[Display omitted] •Canavan disease (CD) is an inherited leukodystrophy resulting from mutations in the ASPA gene.•ASPA deficiency results in severe dysmyelination and a failure of normal brain development.•ASPA catalyzes the cleavage of N-acetylaspartate (NAA) to produce aspartate and acetate.•CD pathogenesis likely involves both NAA accumulation and acetyl-CoA deficiency.•New pharmacological approaches for the treatment of CD are being pursued. Canavan disease (CD) is an inherited leukodystrophy resulting from mutations in the gene encoding aspartoacylase (ASPA). ASPA is highly expressed in oligodendrocytes and catalyzes the cleavage of N-acetylaspartate (NAA) to produce aspartate and acetate. In this review, we examine the pathologies and clinical presentation in CD, the metabolism and transportation of NAA in the brain, and the hypothetical mechanisms whereby ASPA deficiency results in dysmyelination and a failure of normal brain development. We also discuss therapeutic options that could be used for the treatment of CD.