title: Lysosomal enzyme can bypass the blood-brain barrier and reach the CNS following intranasal administration.
abstract: Here we provide the first evidence that therapeutic levels of a lysosomal enzyme can bypass the blood-brain barrier following intranasal administration. α-L-iduronidase (IDUA) activity was detected throughout the brains of IDUA-deficient mice following a single intranasal treatment with concentrated Aldurazyme® (laronidase) and was also detected after intranasal treatment with an adeno-associated virus (AAV) vector expressing human IDUA. These results suggest that intranasal routes of delivery may be efficacious in the treatment of lysosomal storage disorders.
authors.affiliation: Gene Therapy Program, Institute of Human Genetics, Department of Genetics, Cell Biology and Development, University of Minnesota, Minneapolis MN 55455, USA.
authors.forename: Daniel A
authors.initials: DA
authors.lastname: Wolf
authors.forename: Leah R
authors.initials: LR
authors.lastname: Hanson
authors.forename: Elena L
authors.initials: EL
authors.lastname: Aronovich
authors.forename: Zhenhong
authors.initials: Z
authors.lastname: Nan
authors.forename: Walter C
authors.initials: WC
authors.lastname: Low
authors.forename: William H
authors.initials: WH
authors.lastname: Frey
authors.forename: R Scott
authors.initials: RS
authors.lastname: McIvor
mesh_terms: D000281:Administration, Intranasal; D000818:Animals; D001812:Blood-Brain Barrier; D001921:Brain / Q000187:drug effects; D002490:Central Nervous System / Q000187:drug effects*; D000229:Dependovirus / Q000235:genetics; D004195:Disease Models, Animal; D016503:Drug Delivery Systems; D005822:Genetic Vectors / Q000008:administration & dosage; D006801:Humans; D007068:Iduronidase / Q000008:administration & dosage* / Q000235:genetics*; D008247:Lysosomes / Q000201:enzymology; D051379:Mice; D008822:Mice, Transgenic; D008059:Mucopolysaccharidosis I / Q000188:drug therapy*; D011994:Recombinant Proteins / Q000008:administration & dosage
chemical_list: D011994:Recombinant Proteins; D007068:Iduronidase