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Effects of intracerebroventricular administration of 2-hydroxypropyl-β-cyclodextrin in a patient with Niemann–Pick Type C disease

Niemann–Pick Type C disease (NPC) is an autosomal recessive lysosomal storage disorder characterized by progressive neurological deterioration. Previously, we reported that intravenous administration of 2-hydroxypropyl-β-cyclodextrin (HPB-CD) in two patients with NPC had only partial and transient b...

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Autores principales: Matsuo, Muneaki, Shraishi, Koki, Wada, Koki, Ishitsuka, Yoichi, Doi, Hirohito, Maeda, Miyuki, Mizoguchi, Tatsuhiro, Eto, Junya, Mochinaga, Sakiko, Arima, Hidetoshi, Irie, Tetsumi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5121362/
https://www.ncbi.nlm.nih.gov/pubmed/27896112
http://dx.doi.org/10.1016/j.ymgmr.2014.08.004
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author Matsuo, Muneaki
Shraishi, Koki
Wada, Koki
Ishitsuka, Yoichi
Doi, Hirohito
Maeda, Miyuki
Mizoguchi, Tatsuhiro
Eto, Junya
Mochinaga, Sakiko
Arima, Hidetoshi
Irie, Tetsumi
author_facet Matsuo, Muneaki
Shraishi, Koki
Wada, Koki
Ishitsuka, Yoichi
Doi, Hirohito
Maeda, Miyuki
Mizoguchi, Tatsuhiro
Eto, Junya
Mochinaga, Sakiko
Arima, Hidetoshi
Irie, Tetsumi
author_sort Matsuo, Muneaki
collection PubMed
description Niemann–Pick Type C disease (NPC) is an autosomal recessive lysosomal storage disorder characterized by progressive neurological deterioration. Previously, we reported that intravenous administration of 2-hydroxypropyl-β-cyclodextrin (HPB-CD) in two patients with NPC had only partial and transient beneficial effects on neurological function. The most likely reason for HPB-CD not significantly improving the neurological deficits of NPC is its inability to cross the blood–brain barrier. Herein, we describe the effects of intrathecal HPB-CD in an eight-year-old patient with a perinatal onset of NPC, administered initially at a dose of 10 mg/kg every other week and increased up to 10 mg/kg twice a week. Clinically, the patient maintained residual neurological functions for two years, at which time nuclear magnetic resonance spectroscopy showed a decreased choline to creatine ratio and increased N-acetylaspartate to creatine ratio, and positron emission tomography revealed increased standardized uptake values. Total-tau in the cerebrospinal fluid (CSF) was also decreased after two years. No adverse effects were observed over the course of treatment. The CSF concentrations of HPB-CD during the distribution phase after the injections were comparable with those at which HPB-CD could normalize cellular cholesterol abnormality in vitro. Further studies are necessary to elucidate the mechanisms of action of HPB-CD in NPC, and to determine the optimal dose and intervals of HPB-CD injection.
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spelling pubmed-51213622016-11-28 Effects of intracerebroventricular administration of 2-hydroxypropyl-β-cyclodextrin in a patient with Niemann–Pick Type C disease Matsuo, Muneaki Shraishi, Koki Wada, Koki Ishitsuka, Yoichi Doi, Hirohito Maeda, Miyuki Mizoguchi, Tatsuhiro Eto, Junya Mochinaga, Sakiko Arima, Hidetoshi Irie, Tetsumi Mol Genet Metab Rep The Lysosome Niemann–Pick Type C disease (NPC) is an autosomal recessive lysosomal storage disorder characterized by progressive neurological deterioration. Previously, we reported that intravenous administration of 2-hydroxypropyl-β-cyclodextrin (HPB-CD) in two patients with NPC had only partial and transient beneficial effects on neurological function. The most likely reason for HPB-CD not significantly improving the neurological deficits of NPC is its inability to cross the blood–brain barrier. Herein, we describe the effects of intrathecal HPB-CD in an eight-year-old patient with a perinatal onset of NPC, administered initially at a dose of 10 mg/kg every other week and increased up to 10 mg/kg twice a week. Clinically, the patient maintained residual neurological functions for two years, at which time nuclear magnetic resonance spectroscopy showed a decreased choline to creatine ratio and increased N-acetylaspartate to creatine ratio, and positron emission tomography revealed increased standardized uptake values. Total-tau in the cerebrospinal fluid (CSF) was also decreased after two years. No adverse effects were observed over the course of treatment. The CSF concentrations of HPB-CD during the distribution phase after the injections were comparable with those at which HPB-CD could normalize cellular cholesterol abnormality in vitro. Further studies are necessary to elucidate the mechanisms of action of HPB-CD in NPC, and to determine the optimal dose and intervals of HPB-CD injection. Elsevier 2014-09-17 /pmc/articles/PMC5121362/ /pubmed/27896112 http://dx.doi.org/10.1016/j.ymgmr.2014.08.004 Text en © 2014 The Authors http://creativecommons.org/licenses/by-nc-sa/3.0/ This is an open access article under the CC BY-NC-SA license (http://creativecommons.org/licenses/by-nc-sa/3.0/).
spellingShingle The Lysosome
Matsuo, Muneaki
Shraishi, Koki
Wada, Koki
Ishitsuka, Yoichi
Doi, Hirohito
Maeda, Miyuki
Mizoguchi, Tatsuhiro
Eto, Junya
Mochinaga, Sakiko
Arima, Hidetoshi
Irie, Tetsumi
Effects of intracerebroventricular administration of 2-hydroxypropyl-β-cyclodextrin in a patient with Niemann–Pick Type C disease
title Effects of intracerebroventricular administration of 2-hydroxypropyl-β-cyclodextrin in a patient with Niemann–Pick Type C disease
title_full Effects of intracerebroventricular administration of 2-hydroxypropyl-β-cyclodextrin in a patient with Niemann–Pick Type C disease
title_fullStr Effects of intracerebroventricular administration of 2-hydroxypropyl-β-cyclodextrin in a patient with Niemann–Pick Type C disease
title_full_unstemmed Effects of intracerebroventricular administration of 2-hydroxypropyl-β-cyclodextrin in a patient with Niemann–Pick Type C disease
title_short Effects of intracerebroventricular administration of 2-hydroxypropyl-β-cyclodextrin in a patient with Niemann–Pick Type C disease
title_sort effects of intracerebroventricular administration of 2-hydroxypropyl-β-cyclodextrin in a patient with niemann–pick type c disease
topic The Lysosome
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5121362/
https://www.ncbi.nlm.nih.gov/pubmed/27896112
http://dx.doi.org/10.1016/j.ymgmr.2014.08.004
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