In mucopolysaccharidosis type II, a codon-optimized iduronate-2-sulfatase (IDS) construct driven by the MNDU3 promoter achieved supraphysiological enzyme levels across tissues and partial restoration in the brain, normalizing glycosaminoglycan (GAG) accumulation and preventing the emergence of cognitive deficits in vivo [48]. Here, IDS is linked to mucopolysaccharidosis type 2.