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Improvement of CNS Defects Via Continuous Intrathecal Enzyme Replacement by Osmotic Pump in Mucopolysaccharidosis Type II Mice
Author(s) -
Sohn Young Bae,
Lee Jeehun,
Cho Sung Yoon,
Kim Su Jin,
Ko AhRa,
Nam Mi Hyun,
Jin DongKyu
Publication year - 2013
Publication title -
american journal of medical genetics part a
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.064
H-Index - 112
eISSN - 1552-4833
pISSN - 1552-4825
DOI - 10.1002/ajmg.a.35869
Subject(s) - enzyme replacement therapy , mucopolysaccharidosis type ii , lysosomal storage disease , mucopolysaccharidosis , cerebral cortex , glucocerebrosidase , mucopolysaccharidosis i , enzyme , hunter syndrome , chemistry , neun , glycosaminoglycan , thalamus , cortex (anatomy) , medicine , endocrinology , pharmacology , biochemistry , biology , immunohistochemistry , neuroscience , disease , radiology
Mucopolysaccharidosis type II (MPS II), also known as Hunter syndrome (OMIM 309900), is a rare, X‐linked lysosomal storage disorder caused by a deficiency of iduronate‐2‐sulfatase (IDS; EC 3.1.6.13), which is involved in the lysosomal degradation of glycosaminoglycans (GAG). Although intermittent intrathecal (IT) injection of the enzyme has been introduced as a method to overcome the blood‐brain barrier, continuous IT infusion of the enzyme would be more physiologic. This study was performed to investigate responses in the brain of MPS II mice to varying doses of continuous IT infusion of recombinant human IDS (rh‐IDS) in MPS II mice by osmotic pump in three different doses (2.4, 4.8, and 12 µg/day) of rh‐IDS for 3 weeks. The results showed that the group treated with 12 µg/day doses of rh‐IDS demonstrated decreased GAG concentrations compared to the untreated KO mice group ( P = 0.003). After 3 weeks of continuous IT ERT, the brain tissues of the high‐dose IT‐treated KO mice showed a reduction of vacuolation in the cerebral cortex, thalamus and cerebellar cortex, which was not observed in the low‐ and medium‐dose KO mice groups. Moreover, the anti‐NeuN signal representing intact neuron was restored in the cortexes of the high‐dose group. In conclusion, continuous IT infusion of the deficient enzyme was effective in improving CNS defects in the MPS II mice, and could be a valuable therapeutic method for treating neurological deterioration in patients with MPS II. © 2013 Wiley Periodicals, Inc.