Gene Therapy for Neuronopathic Mucopolysaccharidoses: State of the Art

The need for long-lasting and transformative therapies for mucopolysaccharidoses (MPS) cannot be understated. Currently, many forms of MPS lack a specific treatment and in other cases available therapies, such as enzyme replacement therapy (ERT), do not reach important areas such as the central nerv...

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Autores principales: de Castro, María José, del Toro, Mireia, Giugliani, Roberto, Couce, María Luz
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8430935/
https://www.ncbi.nlm.nih.gov/pubmed/34502108
http://dx.doi.org/10.3390/ijms22179200
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author de Castro, María José
del Toro, Mireia
Giugliani, Roberto
Couce, María Luz
author_facet de Castro, María José
del Toro, Mireia
Giugliani, Roberto
Couce, María Luz
author_sort de Castro, María José
collection PubMed
description The need for long-lasting and transformative therapies for mucopolysaccharidoses (MPS) cannot be understated. Currently, many forms of MPS lack a specific treatment and in other cases available therapies, such as enzyme replacement therapy (ERT), do not reach important areas such as the central nervous system (CNS). The advent of newborn screening procedures represents a major step forward in early identification and treatment of individuals with MPS. However, the treatment of brain disease in neuronopathic MPS has been a major challenge to date, mainly because the blood brain barrier (BBB) prevents penetration of the brain by large molecules, including enzymes. Over the last years several novel experimental therapies for neuronopathic MPS have been investigated. Gene therapy and gene editing constitute potentially curative treatments. However, despite recent progress in the field, several considerations should be taken into account. This review focuses on the state of the art of in vivo and ex vivo gene therapy-based approaches targeting the CNS in neuronopathic MPS, discusses clinical trials conducted to date, and provides a vision for the future implications of these therapies for the medical community. Recent advances in the field, as well as limitations relating to efficacy, potential toxicity, and immunogenicity, are also discussed.
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spelling pubmed-84309352021-09-11 Gene Therapy for Neuronopathic Mucopolysaccharidoses: State of the Art de Castro, María José del Toro, Mireia Giugliani, Roberto Couce, María Luz Int J Mol Sci Review The need for long-lasting and transformative therapies for mucopolysaccharidoses (MPS) cannot be understated. Currently, many forms of MPS lack a specific treatment and in other cases available therapies, such as enzyme replacement therapy (ERT), do not reach important areas such as the central nervous system (CNS). The advent of newborn screening procedures represents a major step forward in early identification and treatment of individuals with MPS. However, the treatment of brain disease in neuronopathic MPS has been a major challenge to date, mainly because the blood brain barrier (BBB) prevents penetration of the brain by large molecules, including enzymes. Over the last years several novel experimental therapies for neuronopathic MPS have been investigated. Gene therapy and gene editing constitute potentially curative treatments. However, despite recent progress in the field, several considerations should be taken into account. This review focuses on the state of the art of in vivo and ex vivo gene therapy-based approaches targeting the CNS in neuronopathic MPS, discusses clinical trials conducted to date, and provides a vision for the future implications of these therapies for the medical community. Recent advances in the field, as well as limitations relating to efficacy, potential toxicity, and immunogenicity, are also discussed. MDPI 2021-08-25 /pmc/articles/PMC8430935/ /pubmed/34502108 http://dx.doi.org/10.3390/ijms22179200 Text en © 2021 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
de Castro, María José
del Toro, Mireia
Giugliani, Roberto
Couce, María Luz
Gene Therapy for Neuronopathic Mucopolysaccharidoses: State of the Art
title Gene Therapy for Neuronopathic Mucopolysaccharidoses: State of the Art
title_full Gene Therapy for Neuronopathic Mucopolysaccharidoses: State of the Art
title_fullStr Gene Therapy for Neuronopathic Mucopolysaccharidoses: State of the Art
title_full_unstemmed Gene Therapy for Neuronopathic Mucopolysaccharidoses: State of the Art
title_short Gene Therapy for Neuronopathic Mucopolysaccharidoses: State of the Art
title_sort gene therapy for neuronopathic mucopolysaccharidoses: state of the art
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8430935/
https://www.ncbi.nlm.nih.gov/pubmed/34502108
http://dx.doi.org/10.3390/ijms22179200
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