Making the White Matter Matters: Progress in Understanding Canavan's Disease and Therapeutic Interventions Through...

Canavan's disease (CD) is a fatal autosomal recessive pediatric leukodystrophy in which patients show severe neurodegeneration and typically die by the age of 10, though life expectancy in patients can be highly variable. Currently, there is no effective treatment for CD; however, gene therapy seems to be a feasible approach to combat the disease. Being a monogenic defect, the disease provides an excellent model system to develop gene therapy approaches that can be extended to other monogenic leukodystrophies and neurodegenerative diseases. CD results from mutations in a single gene aspartoacylase which hydrolyses N-acetyl aspartic acid (NAA) which accumulates in its absences. Since CD is one of the few diseases that show high NAA levels, it can also be used to study the enigmatic biological role of NAA. The disease was first described in 1931, and this review traces the progress made in the past 8 decades to understand the disease by enumerating current hypotheses and ongoing palliative measures to alleviate patient symptoms in the context of the latest advances in the field.