Encouraging results in preclinical studies obtained in rodents and large animal models have warranted the development of clinical trials in several LSDs with CNS involvement, namely, MLD, mucopolysaccharidosis (MPSIIIA, MPSIIIB, MPS II, and MPSI), GM1 gangliosidosis, and ceroid lipofuscinosis (CLN2, CLN3, and CLN6). This evidence concerns the gene NAGLU and GM1 gangliosidosis.