Non-genetic therapeutic approaches to Canavan disease

Abstract

Canavan disease (CD) is a rare leukodystrophy characterized by diffuse spongiform white matter degeneration, dysmyelination and intramyelinic oedema with consequent impairment of psychomotor development and early death. The molecular cause of CD has been identified as being mutations of the gene encoding the enzyme aspartoacylase (ASPA) leading to its functional deficiency. The physiological role of ASPA is to hydrolyse N-acetyl-l-aspartic acid (NAA), producing l-aspartic acid and acetate; as a result, its deficiency leads to abnormally high central nervous system NAA levels. The aim of this article is to review what is currently known regarding the aetiopathogenesis and treatment of CD, with emphasis on the non-genetic therapeutic strategies, both at an experimental and a clinical level, by highlighting: (a) major related hypotheses, (b) the results of the available experimental simulatory approaches, as well as (c) the relevance of the so far examined markers of CD neuropathology. The potential and the limitations of the current non-genetic neuroprotective approaches to the treatment of CD are particularly discussed in the current article, in a context that could be used to direct future experimental and (eventually) clinical work in the field.