title: Enzyme-replacement therapy from birth delays the development of behavior and learning problems in mucopolysaccharidosis type IIIA mice.
abstract: Mucopolysaccharidosis type IIIA (MPS IIIA; Sanfilippo syndrome) is a lysosomal storage disorder characterized by severe CNS degeneration, resulting in behavioral abnormalities and loss of learned abilities. Early treatment is vital to prevent long-term clinical pathology in lysosomal storage disorders. We have used naturally occurring MPS IIIA mice to assess the effects of long-term enzyme-replacement therapy initiated either at birth or at 6 wk of age. MPS IIIA and normal control mice received weekly i.v. injections of 1 mg/kg recombinant human sulfamidase until 20 wk of age. Sulfamidase is able to enter the brain until the blood-brain barrier completely closes at 10-14 d of age. MPS IIIA mice that were treated from birth demonstrated normal weight, behavioral characteristics, and ability to learn. MPS IIIA mice that were treated from birth performed significantly better in the Morris water maze than MPS IIIA mice that were treated from 6 wk of age or left untreated. A reduction in storage vacuoles in cells of the CNS in MPS IIIA mice that were treated from birth is consistent with the improvements observed. These data suggest that enzyme that enters the brain in the first few weeks of life, before the blood-brain barrier matures, is able to delay the development of behavior and learning difficulties in MPS IIIA mice.
authors.affiliation: Lysosomal Diseases Research Unit, Women's and Children's Hospital, North Adelaide, South Australia 5006, Australia, briony.gliddon@adelaide.edu.au
authors.forename: Briony L
authors.initials: BL
authors.lastname: Gliddon
authors.forename: John J
authors.initials: JJ
authors.lastname: Hopwood
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D000906:Antibodies / Q000097:blood; D001522:Behavior, Animal / Q000187:drug effects; D001812:Blood-Brain Barrier; D001921:Brain / Q000187:drug effects / Q000473:pathology; D016466:CHO Cells; D006224:Cricetinae; D006867:Hydrolases / Q000276:immunology / Q000493:pharmacokinetics*; D007859:Learning Disabilities / Q000517:prevention & control*; D018782:Maze Learning / Q000187:drug effects; D008568:Memory / Q000187:drug effects; D051379:Mice; D008817:Mice, Mutant Strains; D009084:Mucopolysaccharidosis III / Q000188:drug therapy*; D011994:Recombinant Proteins / Q000276:immunology / Q000493:pharmacokinetics
chemical_list: D000906:Antibodies; D011994:Recombinant Proteins; D006867:Hydrolases; C022708:N-sulfoglucosamine sulfohydrolase