Delivery of therapeutic compounds to the brain and other tissues

摘要

The present invention relates to the intrathecal (IT) administration of recombinant enzyme to treat lysosomal storage disorders. In an exemplary embodiment, intrathecal administration of human α-L-iduronidase (rhIDU) injections in MPS I affected animals resulted in significant enzyme uptake, significant rh-iduronidase activity in brain and meninges and a decrease of glycosaminoglycan (GAG) storage in cells of MPS I subjects to that of normal subjects. Intrathecal administration proved more effective than intravenous treatment at alleviating MPS I symptoms, indicating it is a useful method of treating lysosomal storage disorders.

主权项

1. A method for treating Sanfilippo syndrome type B (Mucopolysaccharidosis type IIIB or MPS IIIB) comprising the step of administering intrathecally to a human subject in need of treatment a pharmaceutical composition comprising a fusion protein comprising recombinant human α-N-acetylglucosaminidase and a moiety that facilitates high uptake of a lysosomal enzyme, wherein the moiety is an IGF-II polypeptide that allows the lysosomal enzyme to bind to the mannose-6-phosphate receptor, and wherein the fusion protein is administered in an amount effective to ameliorate one or more central nervous system (CNS) symptoms of Sanfilippo syndrome type B.