Disclosed herein are recombinant adeno-associated viral vectors expressing aspartoacylase (ASPA) protein and related uses for treating leukodystrophies.

This disclosure provides methods for treating, ameliorating, or reversing at least one symptom of amyotrophic lateral sclerosis (ALS) in a subject by increasing the amount of neuronal aspartate in spinal cord through administration of a therapeutically effective amount of a composition comprising a nucleic acid encoding ASPA or a functional fragment thereof.