Treatment of Sanfilippo syndrome type B by intrathecal administration of alpha-n-acetylglucosaminidase

A method of treating Sanfilippo syndrome type B (San B) disease comprising the steps of:

• intrathecally administering to a subject in need of treating San B disease a pharmaceutical composition comprising a recombinant fusion protein,
• wherein the recombinant fusion protein comprises a lysosomal targeting moiety, an alpha-N-acetylglucosaminidase (Naglu) domain, and a linker between the lysosomal targeting moiety and the Naglu domain,
• wherein the lysosomal targeting moiety is a peptide that binds cation-independent mannose-6-phosphate receptor (CI-MPR) or bis-phosphorylated oligosaccharides,
• wherein the Naglu domain has alpha-N-acetylglucosaminidase activity and comprises an amino acid sequence having at least 90% sequence identity to the amino acid sequence of SEQ ID NO:
• 1, and
• wherein the linker comprises the amino acid sequence of GAPGGGGGAAAAAGGGGGGAPGGGGGGAAAAAGGGGGGAPGGGGGAAAAAGGGGG GAP, which is residues 721-777 of SEQ ID NO:6.