Gene therapy for neuronopathic mucopolysaccharidoses : state of the art
Autor(a) principal: | |
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Data de Publicação: | 2021 |
Outros Autores: | , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Institucional da UFRGS |
Texto Completo: | http://hdl.handle.net/10183/234538 |
Resumo: | 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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Castro, María José deToro, Mireia delGiugliani, RobertoCouce, María Luz2022-01-27T04:34:01Z20211422-0067http://hdl.handle.net/10183/234538001136219The 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.application/pdfengInternational journal of molecular sciences. Basel. Vol. 22 (2021), 9200, 17 p.MucopolissacaridosesSistema nervoso centralTerapia genéticaBarreira hematoencefálicaRevisãoMucopolysaccharidosesGene therapyViral vectorsAdeno-associated virusLentivirusCentral nervous systemBlood brain barrierGene therapy for neuronopathic mucopolysaccharidoses : state of the artEstrangeiroinfo:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/openAccessreponame:Repositório Institucional da UFRGSinstname:Universidade Federal do Rio Grande do Sul (UFRGS)instacron:UFRGSTEXT001136219.pdf.txt001136219.pdf.txtExtracted Texttext/plain78368http://www.lume.ufrgs.br/bitstream/10183/234538/2/001136219.pdf.txt2ba7e2e7bb0f192d725930398dcb812bMD52ORIGINAL001136219.pdfTexto completo (inglês)application/pdf983040http://www.lume.ufrgs.br/bitstream/10183/234538/1/001136219.pdf9e01f3d64ac01db908931024930239faMD5110183/2345382022-02-22 05:07:36.569988oai:www.lume.ufrgs.br:10183/234538Repositório de PublicaçõesPUBhttps://lume.ufrgs.br/oai/requestopendoar:2022-02-22T08:07:36Repositório Institucional da UFRGS - Universidade Federal do Rio Grande do Sul (UFRGS)false |
dc.title.pt_BR.fl_str_mv |
Gene therapy for neuronopathic mucopolysaccharidoses : state of the art |
title |
Gene therapy for neuronopathic mucopolysaccharidoses : state of the art |
spellingShingle |
Gene therapy for neuronopathic mucopolysaccharidoses : state of the art Castro, María José de Mucopolissacaridoses Sistema nervoso central Terapia genética Barreira hematoencefálica Revisão Mucopolysaccharidoses Gene therapy Viral vectors Adeno-associated virus Lentivirus Central nervous system Blood brain barrier |
title_short |
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_sort |
Gene therapy for neuronopathic mucopolysaccharidoses : state of the art |
author |
Castro, María José de |
author_facet |
Castro, María José de Toro, Mireia del Giugliani, Roberto Couce, María Luz |
author_role |
author |
author2 |
Toro, Mireia del Giugliani, Roberto Couce, María Luz |
author2_role |
author author author |
dc.contributor.author.fl_str_mv |
Castro, María José de Toro, Mireia del Giugliani, Roberto Couce, María Luz |
dc.subject.por.fl_str_mv |
Mucopolissacaridoses Sistema nervoso central Terapia genética Barreira hematoencefálica Revisão |
topic |
Mucopolissacaridoses Sistema nervoso central Terapia genética Barreira hematoencefálica Revisão Mucopolysaccharidoses Gene therapy Viral vectors Adeno-associated virus Lentivirus Central nervous system Blood brain barrier |
dc.subject.eng.fl_str_mv |
Mucopolysaccharidoses Gene therapy Viral vectors Adeno-associated virus Lentivirus Central nervous system Blood brain barrier |
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. |
publishDate |
2021 |
dc.date.issued.fl_str_mv |
2021 |
dc.date.accessioned.fl_str_mv |
2022-01-27T04:34:01Z |
dc.type.driver.fl_str_mv |
Estrangeiro info:eu-repo/semantics/article |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
format |
article |
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publishedVersion |
dc.identifier.uri.fl_str_mv |
http://hdl.handle.net/10183/234538 |
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1422-0067 |
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001136219 |
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http://hdl.handle.net/10183/234538 |
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eng |
language |
eng |
dc.relation.ispartof.pt_BR.fl_str_mv |
International journal of molecular sciences. Basel. Vol. 22 (2021), 9200, 17 p. |
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info:eu-repo/semantics/openAccess |
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openAccess |
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