Current status of gene therapy research in polyglutamine spinocerebellar ataxias
Autor(a) principal: | |
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Data de Publicação: | 2021 |
Outros Autores: | , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
Texto Completo: | http://hdl.handle.net/10400.1/15439 |
Resumo: | Polyglutamine spinocerebellar ataxias (PolyQ SCAs) are a group of 6 rare autosomal dominant diseases, which arise from an abnormal CAG repeat expansion in the coding region of their causative gene. These neurodegenerative ataxic disorders are characterized by progressive cerebellar degeneration, which translates into progressive ataxia, the main clinical feature, often accompanied by oculomotor deficits and dysarthria. Currently, PolyQ SCAs treatment is limited only to symptomatic mitigation, and no therapy is available to stop or delay the disease progression, which culminates with death. Over the last years, many promising gene therapy approaches were investigated in preclinical studies and could lead to a future treatment to stop or delay the disease development. Here, we summed up the most promising of these therapies, categorizing them in gene augmentation therapy, gene silencing strategies, and gene edition approaches. While several of the reviewed strategies are promising, there is still a gap from the preclinical results obtained and their translation to clinical studies. However, there is an increase in the number of approved gene therapies, as well as a constant development in their safety and efficacy profiles. Thus, it is expected that in a near future some of the promising strategies reviewed here could be tested in a clinical setting and if successful provide hope for SCAs patients. |
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Current status of gene therapy research in polyglutamine spinocerebellar ataxiasPolyglutamine disordersSpinocerebellar ataxiaGene therapyGene augmentationGene silencingGene editingPolyglutamine spinocerebellar ataxias (PolyQ SCAs) are a group of 6 rare autosomal dominant diseases, which arise from an abnormal CAG repeat expansion in the coding region of their causative gene. These neurodegenerative ataxic disorders are characterized by progressive cerebellar degeneration, which translates into progressive ataxia, the main clinical feature, often accompanied by oculomotor deficits and dysarthria. Currently, PolyQ SCAs treatment is limited only to symptomatic mitigation, and no therapy is available to stop or delay the disease progression, which culminates with death. Over the last years, many promising gene therapy approaches were investigated in preclinical studies and could lead to a future treatment to stop or delay the disease development. Here, we summed up the most promising of these therapies, categorizing them in gene augmentation therapy, gene silencing strategies, and gene edition approaches. While several of the reviewed strategies are promising, there is still a gap from the preclinical results obtained and their translation to clinical studies. However, there is an increase in the number of approved gene therapies, as well as a constant development in their safety and efficacy profiles. Thus, it is expected that in a near future some of the promising strategies reviewed here could be tested in a clinical setting and if successful provide hope for SCAs patients.Foundation (FCT) project (ALG-01-0145-FEDER-29480)MDPISapientiaAfonso-Reis, RicardoAfonso, Inês T.Nóbrega, Clévio2021-04-26T08:48:21Z2021-04-192021-04-23T13:31:51Z2021-04-19T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10400.1/15439engInternational Journal of Molecular Sciences 22 (8): 4249 (2021)10.3390/ijms220842491422-0067info:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2023-07-24T10:27:51Zoai:sapientia.ualg.pt:10400.1/15439Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T20:06:16.428807Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse |
dc.title.none.fl_str_mv |
Current status of gene therapy research in polyglutamine spinocerebellar ataxias |
title |
Current status of gene therapy research in polyglutamine spinocerebellar ataxias |
spellingShingle |
Current status of gene therapy research in polyglutamine spinocerebellar ataxias Afonso-Reis, Ricardo Polyglutamine disorders Spinocerebellar ataxia Gene therapy Gene augmentation Gene silencing Gene editing |
title_short |
Current status of gene therapy research in polyglutamine spinocerebellar ataxias |
title_full |
Current status of gene therapy research in polyglutamine spinocerebellar ataxias |
title_fullStr |
Current status of gene therapy research in polyglutamine spinocerebellar ataxias |
title_full_unstemmed |
Current status of gene therapy research in polyglutamine spinocerebellar ataxias |
title_sort |
Current status of gene therapy research in polyglutamine spinocerebellar ataxias |
author |
Afonso-Reis, Ricardo |
author_facet |
Afonso-Reis, Ricardo Afonso, Inês T. Nóbrega, Clévio |
author_role |
author |
author2 |
Afonso, Inês T. Nóbrega, Clévio |
author2_role |
author author |
dc.contributor.none.fl_str_mv |
Sapientia |
dc.contributor.author.fl_str_mv |
Afonso-Reis, Ricardo Afonso, Inês T. Nóbrega, Clévio |
dc.subject.por.fl_str_mv |
Polyglutamine disorders Spinocerebellar ataxia Gene therapy Gene augmentation Gene silencing Gene editing |
topic |
Polyglutamine disorders Spinocerebellar ataxia Gene therapy Gene augmentation Gene silencing Gene editing |
description |
Polyglutamine spinocerebellar ataxias (PolyQ SCAs) are a group of 6 rare autosomal dominant diseases, which arise from an abnormal CAG repeat expansion in the coding region of their causative gene. These neurodegenerative ataxic disorders are characterized by progressive cerebellar degeneration, which translates into progressive ataxia, the main clinical feature, often accompanied by oculomotor deficits and dysarthria. Currently, PolyQ SCAs treatment is limited only to symptomatic mitigation, and no therapy is available to stop or delay the disease progression, which culminates with death. Over the last years, many promising gene therapy approaches were investigated in preclinical studies and could lead to a future treatment to stop or delay the disease development. Here, we summed up the most promising of these therapies, categorizing them in gene augmentation therapy, gene silencing strategies, and gene edition approaches. While several of the reviewed strategies are promising, there is still a gap from the preclinical results obtained and their translation to clinical studies. However, there is an increase in the number of approved gene therapies, as well as a constant development in their safety and efficacy profiles. Thus, it is expected that in a near future some of the promising strategies reviewed here could be tested in a clinical setting and if successful provide hope for SCAs patients. |
publishDate |
2021 |
dc.date.none.fl_str_mv |
2021-04-26T08:48:21Z 2021-04-19 2021-04-23T13:31:51Z 2021-04-19T00:00:00Z |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
format |
article |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
http://hdl.handle.net/10400.1/15439 |
url |
http://hdl.handle.net/10400.1/15439 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
International Journal of Molecular Sciences 22 (8): 4249 (2021) 10.3390/ijms22084249 1422-0067 |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
application/pdf |
dc.publisher.none.fl_str_mv |
MDPI |
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MDPI |
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reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação instacron:RCAAP |
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Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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RCAAP |
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RCAAP |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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1799133303647764480 |