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Correction of CNS defects in the MPSII mouse model via systemic enzyme replacement therapy

Mucopolysaccharidosis type II (MPSII), or Hunter syndrome, is a devastating disorder associated with a shortened life expectancy. Patients affected by MPSII have a variety of symptoms that affect all organs of the body and may include progressive cognitive impairment. MPSII is due to inactivity of t...

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Autores principales: Polito, Vinicia Assunta, Abbondante, Serena, Polishchuk, Roman S., Nusco, Edoardo, Salvia, Rosaria, Cosma, Maria Pia
Formato: Texto
Lenguaje:English
Publicado: Oxford University Press 2010
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2989894/
https://www.ncbi.nlm.nih.gov/pubmed/20876612
http://dx.doi.org/10.1093/hmg/ddq420
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author Polito, Vinicia Assunta
Abbondante, Serena
Polishchuk, Roman S.
Nusco, Edoardo
Salvia, Rosaria
Cosma, Maria Pia
author_facet Polito, Vinicia Assunta
Abbondante, Serena
Polishchuk, Roman S.
Nusco, Edoardo
Salvia, Rosaria
Cosma, Maria Pia
author_sort Polito, Vinicia Assunta
collection PubMed
description Mucopolysaccharidosis type II (MPSII), or Hunter syndrome, is a devastating disorder associated with a shortened life expectancy. Patients affected by MPSII have a variety of symptoms that affect all organs of the body and may include progressive cognitive impairment. MPSII is due to inactivity of the enzyme iduronate-2-sulfatase (IDS), which results in the accumulation of storage material in the lysosomes, such as dermatan and heparan sulfates, with consequent cell degeneration in all tissues including, in the severe phenotype, neurodegeneration in the central nervous system (CNS). To date, the only treatment available is systemic infusion of IDS, which ameliorates exclusively certain visceral defects. Therefore, it is important to simultaneously treat the visceral and CNS defects of the MPSII patients. Here, we have developed enzyme replacement therapy (ERT) protocols in a mouse model that allow the IDS to reach the brain, with the substantial correction of the CNS phenotype and of the neurobehavioral features. Treatments were beneficial even in adult and old MPSII mice, using relatively low doses of infused IDS over long intervals. This study demonstrates that CNS defects of MPSII mice can be treated by systemic ERT, providing the potential for development of an effective treatment for MPSII patients.
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spelling pubmed-29898942010-11-23 Correction of CNS defects in the MPSII mouse model via systemic enzyme replacement therapy Polito, Vinicia Assunta Abbondante, Serena Polishchuk, Roman S. Nusco, Edoardo Salvia, Rosaria Cosma, Maria Pia Hum Mol Genet Articles Mucopolysaccharidosis type II (MPSII), or Hunter syndrome, is a devastating disorder associated with a shortened life expectancy. Patients affected by MPSII have a variety of symptoms that affect all organs of the body and may include progressive cognitive impairment. MPSII is due to inactivity of the enzyme iduronate-2-sulfatase (IDS), which results in the accumulation of storage material in the lysosomes, such as dermatan and heparan sulfates, with consequent cell degeneration in all tissues including, in the severe phenotype, neurodegeneration in the central nervous system (CNS). To date, the only treatment available is systemic infusion of IDS, which ameliorates exclusively certain visceral defects. Therefore, it is important to simultaneously treat the visceral and CNS defects of the MPSII patients. Here, we have developed enzyme replacement therapy (ERT) protocols in a mouse model that allow the IDS to reach the brain, with the substantial correction of the CNS phenotype and of the neurobehavioral features. Treatments were beneficial even in adult and old MPSII mice, using relatively low doses of infused IDS over long intervals. This study demonstrates that CNS defects of MPSII mice can be treated by systemic ERT, providing the potential for development of an effective treatment for MPSII patients. Oxford University Press 2010-12-15 2010-09-27 /pmc/articles/PMC2989894/ /pubmed/20876612 http://dx.doi.org/10.1093/hmg/ddq420 Text en © The Author 2010. Published by Oxford University Press. http://creativecommons.org/licenses/by-nc/2.5/ This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/2.5), which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Articles
Polito, Vinicia Assunta
Abbondante, Serena
Polishchuk, Roman S.
Nusco, Edoardo
Salvia, Rosaria
Cosma, Maria Pia
Correction of CNS defects in the MPSII mouse model via systemic enzyme replacement therapy
title Correction of CNS defects in the MPSII mouse model via systemic enzyme replacement therapy
title_full Correction of CNS defects in the MPSII mouse model via systemic enzyme replacement therapy
title_fullStr Correction of CNS defects in the MPSII mouse model via systemic enzyme replacement therapy
title_full_unstemmed Correction of CNS defects in the MPSII mouse model via systemic enzyme replacement therapy
title_short Correction of CNS defects in the MPSII mouse model via systemic enzyme replacement therapy
title_sort correction of cns defects in the mpsii mouse model via systemic enzyme replacement therapy
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2989894/
https://www.ncbi.nlm.nih.gov/pubmed/20876612
http://dx.doi.org/10.1093/hmg/ddq420
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