TY - JOUR
T1 - Intrathecal enzyme replacement therapy reverses cognitive decline in mucopolysaccharidosis type I
AU - Nestrasil, Igor
AU - Shapiro, Elsa
AU - Svatkova, Alena
AU - Dickson, Patricia
AU - Chen, Agnes
AU - Wakumoto, Amy
AU - Ahmed, Alia
AU - Stehel, Edward
AU - McNeil, Sarah
AU - Gravance, Curtis
AU - Maher, Elizabeth
N1 - Funding Information:
Funding for this study was provided by The Ryan Foundation (a private MPS I family charitable organization), BioMarin Pharmaceutical, Inc., and the Lysosomal Disease Network. The Lysosomal Disease Network (U54NS065768) is a part of the National Institutes of Health (NIH) Rare Diseases Clinical Research Network (RDCRN), supported through collaboration between the NIH Office of Rare Diseases Research (ORDR) at the National Center for Advancing Translational Science (NCATS), the National Institute of Neurological Disorders and Stroke (NINDS), and National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Additional support was received from National Center for Advancing Translational Sciences of the National Institutes of Health Award Number UL1TR000114 and by the project “CEITEC 2020 (LQ1601)” from the Ministry of Education, Youth and Sports of the Czech Republic (to AS).
Publisher Copyright:
© 2017 Wiley Periodicals, Inc.
PY - 2017/3/1
Y1 - 2017/3/1
N2 - 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.
AB - 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.
KW - blood-brain barrier
KW - brain
KW - diffusion tensor imaging
KW - enzyme replacement therapy
KW - intrathecal administration
KW - magnetic resonance imaging
KW - mucopolysaccharidosis
KW - neuropsychology
UR - http://www.scopus.com/inward/record.url?scp=85013220493&partnerID=8YFLogxK
U2 - 10.1002/ajmg.a.38073
DO - 10.1002/ajmg.a.38073
M3 - Article
C2 - 28211988
AN - SCOPUS:85013220493
VL - 173
SP - 780
EP - 783
JO - American Journal of Medical Genetics, Part A
JF - American Journal of Medical Genetics, Part A
SN - 1552-4825
IS - 3
ER -