title: Intrathecal enzyme replacement therapy reverses cognitive decline in mucopolysaccharidosis type I.
abstract: Mucopolysaccharidosis type I (MPS I) is an inherited lysosomal storage disease that seriously affects the brain. Severity of neurocognitive symptoms in attenuated MPS subtype (MPS IA) broadly varies partially, due to restricted permeability of blood-brain barrier (BBB) which limits treatment effects of intravenously applied α-L-iduronidase (rhIDU) enzyme. Intrathecal (IT) rhIDU application as a possible solution to circumvent BBB improved brain outcomes in canine models; therefore, our study quantifies effects of IT rhIDU on brain structure and function in an MPS IA patient with previous progressive cognitive decline. Neuropsychological testing and MRIs were performed twice prior (baseline, at 1 year) and twice after initiating IT rhIDU (at 2nd and 3rd years). The difference between pre- and post-treatment means was evaluated as a percentage of the change. Neurocognitive performance improved particularly in memory tests and resulted in improved school performance after IT rhIDU treatment. White matter (WM) integrity improved together with an increase of WM and corpus callosum volumes. Hippocampal and gray matter volume decreased which may either parallel reduction of glycosaminoglycan storage or reflect typical longitudinal brain changes in early adulthood. In conclusion, our outcomes suggest neurological benefits of IT rhIDU compared to the intravenous administration on brain structure and function in a single MPS IA patient.© 2017 Wiley Periodicals, Inc.
authors.affiliation: University of Minnesota, Minneapolis, Minnesota.
authors.forename: Igor
authors.initials: I
authors.lastname: Nestrasil
authors.affiliation: University of Minnesota, Minneapolis, Minnesota.
authors.forename: Elsa
authors.initials: E
authors.lastname: Shapiro
authors.affiliation: University of Minnesota, Minneapolis, Minnesota.|Multimodal and Functional Neuroimaging Research Group, CEITEC-Central European Institute of Technology, Masaryk University, Brno, Czech Republic.
authors.forename: Alena
authors.initials: A
authors.lastname: Svatkova
authors.affiliation: Los Angeles Biomedical Institute at Harbor-UCLA, Torrance, California.
authors.forename: Patricia
authors.initials: P
authors.lastname: Dickson
authors.affiliation: Los Angeles Biomedical Institute at Harbor-UCLA, Torrance, California.
authors.forename: Agnes
authors.initials: A
authors.lastname: Chen
authors.affiliation: University of Minnesota, Minneapolis, Minnesota.
authors.forename: Amy
authors.initials: A
authors.lastname: Wakumoto
authors.affiliation: University of Minnesota, Minneapolis, Minnesota.
authors.forename: Alia
authors.initials: A
authors.lastname: Ahmed
authors.affiliation: University of Texas Southwestern Medical Center, Dallas, Texas.
authors.forename: Edward
authors.initials: E
authors.lastname: Stehel
authors.affiliation: University of Texas Southwestern Medical Center, Dallas, Texas.
authors.forename: Sarah
authors.initials: S
authors.lastname: McNeil
authors.affiliation: Ryan Foundation, Carrollton, Texas.
authors.forename: Curtis
authors.initials: C
authors.lastname: Gravance
authors.affiliation: University of Texas Southwestern Medical Center, Dallas, Texas.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Maher
mesh_terms: D060825:Cognitive Dysfunction / Q000188:drug therapy*; D056947:Enzyme Replacement Therapy / Q000009:adverse effects / Q000379:methods; D006801:Humans; D007068:Iduronidase / Q000008:administration & dosage* / Q000009:adverse effects; D007278:Injections, Spinal; D008279:Magnetic Resonance Imaging; D008297:Male; D008059:Mucopolysaccharidosis I / Q000175:diagnosis / Q000188:drug therapy* / Q000523:psychology*; D009483:Neuropsychological Tests; D010641:Phenotype; D016896:Treatment Outcome; D066127:White Matter / Q000187:drug effects / Q000473:pathology; D055815:Young Adult
chemical_list: D007068:Iduronidase
keywords: blood-brain barrier; brain; diffusion tensor imaging; enzyme replacement therapy; intrathecal administration; magnetic resonance imaging; mucopolysaccharidosis; neuropsychology