In some aspects, the disclosure relates to compositions and methods useful forthe diagnosis and treatment ofneuro-degenerative diseases, such as leukodystrophies (e.g., Canavan Disease).In some embodiments, the methods comprise administeringto a subject an N-acetylaspartate (NAA)-depleting agent or an N-acetylaspartate (NAA)-depleting agent based upon the subject'smetabolic profile.