The present disclosure relates to compositions for use in a method of treating Sanfilippo syndrome (also known as Sanfilippo disease type D, Sanfilippo D, mucopolysaccharidosis type IIID, MPS IIID). The method can entail injecting to the spinal fluid of a MPS IIID patient an effective amount of a composition comprising a recombinant human acetylglucosamine-6-sulfatase (GNS) protein comprising the amino acid sequence of SEQ ID NO: 1 or an amino acid sequence having at least 90% sequence identity to SEQ ID NO: 1 and having the enzymatic activity of the human GNS protein. The composition can be tested in a testing buffer comprising less than 500 mM sodium, less than 100 mM citrate, less than 100 mM phosphate, less than 100 mM sulfate, and at least 0.005% Triton X-100 at a pH of about 5.6.