Lysosomal enzyme can bypass the blood-brain barrier and reach the CNS following intranasal administration

Mol Genet Metab. 2012 May;106(1):131-4. doi: 10.1016/j.ymgme.2012.02.006. Epub 2012 Feb 10.

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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Administration, Intranasal
  • Animals
  • Blood-Brain Barrier*
  • Brain / drug effects
  • Central Nervous System / drug effects*
  • Dependovirus / genetics
  • Disease Models, Animal
  • Drug Delivery Systems
  • Genetic Vectors / administration & dosage
  • Humans
  • Iduronidase / administration & dosage*
  • Iduronidase / genetics*
  • Lysosomes / enzymology
  • Mice
  • Mice, Transgenic
  • Mucopolysaccharidosis I / drug therapy*
  • Recombinant Proteins / administration & dosage

Substances

  • Recombinant Proteins
  • Iduronidase