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Enzyme replacement therapy (ERT) procedure for mucopolysaccharidosis type II (MPS II) by intraventricular administration (IVA) in murine MPS II.
Mol Genet Metab 2012; 107(1-2):122-8MG

Abstract

Mucopolysaccharidosis type II (MPS II), or Hunter syndrome, is a lysosomal storage disorder caused by a deficiency of iduronate-2-sulfatase (IDS) and is characterized by the accumulation of glycosaminoglycans (GAGs). MPS II has been treated by hematopoietic stem cell therapy (HSCT)/enzyme replacement therapy (ERT), but its effectiveness in the central nervous system (CNS) is limited because of poor enzyme uptake across the blood-brain barrier (BBB). To increase the efficacy of ERT in the brain, we tested an intraventricular ERT procedure consisting of repeated administrations of IDS (20 μg/mouse/3 weeks) in IDS-knockout, MPS II model mice. The IDS enzyme activity and the accumulation of total GAGs were measured in mouse brains. The IDS activity was significantly increased, and the accumulation of total GAGs was decreased in the MPS II mouse brains treated with multiple administrations of IDS via intraventricular ERT. Additionally, a high level of IDS enzyme activity was appreciated in other MPS II mouse tissues, such as the liver, spleen, testis and others. A Y-maze was used to test learning and memory after repeated intraventricular ERT with IDS. The IDS-treated mouse groups recovered the capacity for short-term memory and activity. Although large and small vacuoles were found at the margin of the cerebellar Purkinje cells in the disease-control mice, these vacuoles disappeared upon treated with IDS. Loss of vacuoles was also observed in other tissues (liver, kidney and testis). These results demonstrate the possible efficacy of an ERT procedure with intraventricular administration of IDS for the treatment of MPS II.

Authors+Show Affiliations

Department of Genetic Diseases & Genomic Science, The Jikei University School of Medicine, Tokyo, Japan.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

22704483

Citation

Higuchi, Takashi, et al. "Enzyme Replacement Therapy (ERT) Procedure for Mucopolysaccharidosis Type II (MPS II) By Intraventricular Administration (IVA) in Murine MPS II." Molecular Genetics and Metabolism, vol. 107, no. 1-2, 2012, pp. 122-8.
Higuchi T, Shimizu H, Fukuda T, et al. Enzyme replacement therapy (ERT) procedure for mucopolysaccharidosis type II (MPS II) by intraventricular administration (IVA) in murine MPS II. Mol Genet Metab. 2012;107(1-2):122-8.
Higuchi, T., Shimizu, H., Fukuda, T., Kawagoe, S., Matsumoto, J., Shimada, Y., ... Eto, Y. (2012). Enzyme replacement therapy (ERT) procedure for mucopolysaccharidosis type II (MPS II) by intraventricular administration (IVA) in murine MPS II. Molecular Genetics and Metabolism, 107(1-2), pp. 122-8. doi:10.1016/j.ymgme.2012.05.005.
Higuchi T, et al. Enzyme Replacement Therapy (ERT) Procedure for Mucopolysaccharidosis Type II (MPS II) By Intraventricular Administration (IVA) in Murine MPS II. Mol Genet Metab. 2012;107(1-2):122-8. PubMed PMID: 22704483.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Enzyme replacement therapy (ERT) procedure for mucopolysaccharidosis type II (MPS II) by intraventricular administration (IVA) in murine MPS II. AU - Higuchi,Takashi, AU - Shimizu,Hiromi, AU - Fukuda,Takahiro, AU - Kawagoe,Shiho, AU - Matsumoto,Juri, AU - Shimada,Yohta, AU - Kobayashi,Hiroshi, AU - Ida,Hiroyuki, AU - Ohashi,Toya, AU - Morimoto,Hideto, AU - Hirato,Tohru, AU - Nishino,Katsuya, AU - Eto,Yoshikatsu, Y1 - 2012/05/18/ PY - 2012/03/08/received PY - 2012/05/01/revised PY - 2012/05/02/accepted PY - 2012/6/19/entrez PY - 2012/6/19/pubmed PY - 2013/1/30/medline SP - 122 EP - 8 JF - Molecular genetics and metabolism JO - Mol. Genet. Metab. VL - 107 IS - 1-2 N2 - Mucopolysaccharidosis type II (MPS II), or Hunter syndrome, is a lysosomal storage disorder caused by a deficiency of iduronate-2-sulfatase (IDS) and is characterized by the accumulation of glycosaminoglycans (GAGs). MPS II has been treated by hematopoietic stem cell therapy (HSCT)/enzyme replacement therapy (ERT), but its effectiveness in the central nervous system (CNS) is limited because of poor enzyme uptake across the blood-brain barrier (BBB). To increase the efficacy of ERT in the brain, we tested an intraventricular ERT procedure consisting of repeated administrations of IDS (20 μg/mouse/3 weeks) in IDS-knockout, MPS II model mice. The IDS enzyme activity and the accumulation of total GAGs were measured in mouse brains. The IDS activity was significantly increased, and the accumulation of total GAGs was decreased in the MPS II mouse brains treated with multiple administrations of IDS via intraventricular ERT. Additionally, a high level of IDS enzyme activity was appreciated in other MPS II mouse tissues, such as the liver, spleen, testis and others. A Y-maze was used to test learning and memory after repeated intraventricular ERT with IDS. The IDS-treated mouse groups recovered the capacity for short-term memory and activity. Although large and small vacuoles were found at the margin of the cerebellar Purkinje cells in the disease-control mice, these vacuoles disappeared upon treated with IDS. Loss of vacuoles was also observed in other tissues (liver, kidney and testis). These results demonstrate the possible efficacy of an ERT procedure with intraventricular administration of IDS for the treatment of MPS II. SN - 1096-7206 UR - https://www.unboundmedicine.com/medline/citation/22704483/Enzyme_replacement_therapy__ERT__procedure_for_mucopolysaccharidosis_type_II__MPS_II__by_intraventricular_administration__IVA__in_murine_MPS_II_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S1096-7192(12)00194-1 DB - PRIME DP - Unbound Medicine ER -