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Treatment of Neuronopathic Mucopolysaccharidoses with Blood–Brain Barrier-Crossing Enzymes: Clinical Application of Receptor-Mediated Transcytosis
Enzyme replacement therapy (ERT) has paved the way for treating the somatic symptoms of lysosomal storage diseases (LSDs), but the inability of intravenously administered enzymes to cross the blood–brain barrier (BBB) has left the central nervous system (CNS)-related symptoms of LSDs largely impervi...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9229961/ https://www.ncbi.nlm.nih.gov/pubmed/35745811 http://dx.doi.org/10.3390/pharmaceutics14061240 |
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author | Sonoda, Hiroyuki Takahashi, Kenichi Minami, Kohtaro Hirato, Toru Yamamoto, Tatsuyoshi So, Sairei Tanizawa, Kazunori Schmidt, Mathias Sato, Yuji |
author_facet | Sonoda, Hiroyuki Takahashi, Kenichi Minami, Kohtaro Hirato, Toru Yamamoto, Tatsuyoshi So, Sairei Tanizawa, Kazunori Schmidt, Mathias Sato, Yuji |
author_sort | Sonoda, Hiroyuki |
collection | PubMed |
description | Enzyme replacement therapy (ERT) has paved the way for treating the somatic symptoms of lysosomal storage diseases (LSDs), but the inability of intravenously administered enzymes to cross the blood–brain barrier (BBB) has left the central nervous system (CNS)-related symptoms of LSDs largely impervious to the therapeutic benefits of ERT, although ERT via intrathecal and intracerebroventricular routes can be used for some neuronopathic LSDs (in particular, mucopolysaccharidoses). However, the considerable practical issues involved make these routes unsuitable for long-term treatment. Efforts have been made to modify enzymes (e.g., by fusing them with antibodies against innate receptors on the cerebrovascular endothelium) so that they can cross the BBB via receptor-mediated transcytosis (RMT) and address neuronopathy in the CNS. This review summarizes the various scientific and technological challenges of applying RMT to the development of safe and effective enzyme therapeutics for neuronopathic mucopolysaccharidoses; it then discusses the translational and methodological issues surrounding preclinical and clinical evaluation to establish RMT-applied ERT. |
format | Online Article Text |
id | pubmed-9229961 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-92299612022-06-25 Treatment of Neuronopathic Mucopolysaccharidoses with Blood–Brain Barrier-Crossing Enzymes: Clinical Application of Receptor-Mediated Transcytosis Sonoda, Hiroyuki Takahashi, Kenichi Minami, Kohtaro Hirato, Toru Yamamoto, Tatsuyoshi So, Sairei Tanizawa, Kazunori Schmidt, Mathias Sato, Yuji Pharmaceutics Review Enzyme replacement therapy (ERT) has paved the way for treating the somatic symptoms of lysosomal storage diseases (LSDs), but the inability of intravenously administered enzymes to cross the blood–brain barrier (BBB) has left the central nervous system (CNS)-related symptoms of LSDs largely impervious to the therapeutic benefits of ERT, although ERT via intrathecal and intracerebroventricular routes can be used for some neuronopathic LSDs (in particular, mucopolysaccharidoses). However, the considerable practical issues involved make these routes unsuitable for long-term treatment. Efforts have been made to modify enzymes (e.g., by fusing them with antibodies against innate receptors on the cerebrovascular endothelium) so that they can cross the BBB via receptor-mediated transcytosis (RMT) and address neuronopathy in the CNS. This review summarizes the various scientific and technological challenges of applying RMT to the development of safe and effective enzyme therapeutics for neuronopathic mucopolysaccharidoses; it then discusses the translational and methodological issues surrounding preclinical and clinical evaluation to establish RMT-applied ERT. MDPI 2022-06-11 /pmc/articles/PMC9229961/ /pubmed/35745811 http://dx.doi.org/10.3390/pharmaceutics14061240 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Review Sonoda, Hiroyuki Takahashi, Kenichi Minami, Kohtaro Hirato, Toru Yamamoto, Tatsuyoshi So, Sairei Tanizawa, Kazunori Schmidt, Mathias Sato, Yuji Treatment of Neuronopathic Mucopolysaccharidoses with Blood–Brain Barrier-Crossing Enzymes: Clinical Application of Receptor-Mediated Transcytosis |
title | Treatment of Neuronopathic Mucopolysaccharidoses with Blood–Brain Barrier-Crossing Enzymes: Clinical Application of Receptor-Mediated Transcytosis |
title_full | Treatment of Neuronopathic Mucopolysaccharidoses with Blood–Brain Barrier-Crossing Enzymes: Clinical Application of Receptor-Mediated Transcytosis |
title_fullStr | Treatment of Neuronopathic Mucopolysaccharidoses with Blood–Brain Barrier-Crossing Enzymes: Clinical Application of Receptor-Mediated Transcytosis |
title_full_unstemmed | Treatment of Neuronopathic Mucopolysaccharidoses with Blood–Brain Barrier-Crossing Enzymes: Clinical Application of Receptor-Mediated Transcytosis |
title_short | Treatment of Neuronopathic Mucopolysaccharidoses with Blood–Brain Barrier-Crossing Enzymes: Clinical Application of Receptor-Mediated Transcytosis |
title_sort | treatment of neuronopathic mucopolysaccharidoses with blood–brain barrier-crossing enzymes: clinical application of receptor-mediated transcytosis |
topic | Review |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9229961/ https://www.ncbi.nlm.nih.gov/pubmed/35745811 http://dx.doi.org/10.3390/pharmaceutics14061240 |
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