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Gene Therapies for Polyglutamine Diseases

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Polyglutamine Disorders

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 1049))

Abstract

Polyglutamine diseases are hereditary degenerative disorders of the nervous system that have remained, to this date, untreatable. Promisingly, investigation into their molecular etiology and the development of increasingly perfected tools have contributed to the design of novel strategies with therapeutic potential. Encouraging studies have explored gene therapy as a means to counteract cell demise and loss in this context. The current chapter addresses the two main focuses of research in the area: the characteristics of the systems used to deliver nucleic acids to cells and the molecular and cellular actions of the therapeutic agents. Vectors used in gene therapy have to satisfyingly reach the tissues and cell types of interest, while eliciting the lowest toxicity possible. Both viral and non-viral systems have been developed for the delivery of nucleic acids to the central nervous system, each with its respective advantages and shortcomings. Since each polyglutamine disease is caused by mutation of a single gene, many gene therapy strategies have tried to halt degeneration by silencing the corresponding protein products, usually recurring to RNA interference. The potential of small interfering RNAs, short hairpin RNAs and microRNAs has been investigated. Overexpression of protective genes has also been evaluated as a means of decreasing mutant protein toxicity and operate beneficial alterations. Recent gene editing tools promise yet other ways of interfering with the disease-causing genes, at the most upstream points possible. Results obtained in both cell and animal models encourage further delving into this type of therapeutic strategies and support the future use of gene therapy in the treatment of polyglutamine diseases.

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Authors and Affiliations

  1. CNC—Center for Neuroscience and Cell Biology, University of Coimbra, Coimbra, Portugal

    Carlos A. Matos, Vítor Carmona, Udaya-Geetha Vijayakumar, Sara Lopes, Patrícia Albuquerque, Mariana Conceição, Rui Jorge Nobre, Clévio Nóbrega & Luís Pereira de Almeida

  2. Institute for Interdisciplinary Research, University of Coimbra, Coimbra, Portugal

    Carlos A. Matos, Sara Lopes & Rui Jorge Nobre

  3. Faculty of Pharmacy, University of Coimbra, Coimbra, Portugal

    Vítor Carmona, Patrícia Albuquerque & Luís Pereira de Almeida

  4. Department of Biomedical Sciences and Medicine, University of Algarve, Faro, Portugal

    Clévio Nóbrega

  5. Centre for Biomedical Research, University of Algarve, Faro, Portugal

    Clévio Nóbrega

  6. Algarve Biomedical Center, University of Algarve, Faro, Portugal

    Clévio Nóbrega

Authors
  1. Carlos A. Matos
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  2. Vítor Carmona
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  3. Udaya-Geetha Vijayakumar
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  4. Sara Lopes
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  5. Patrícia Albuquerque
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  6. Mariana Conceição
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  7. Rui Jorge Nobre
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  8. Clévio Nóbrega
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  9. Luís Pereira de Almeida
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Corresponding author

Correspondence to Luís Pereira de Almeida .

Editor information

Editors and Affiliations

  1. Department of Biomedical Sciences and Medicine; Centre for Biomedical Research and Algarve Biomedical Center, University of Algarve, Faro, Portugal

    Clévio Nóbrega

  2. Center for Neuroscience and Cell Biology and Faculty of Pharmacy, University of Coimbra, Coimbra, Portugal

    Luís Pereira de Almeida

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Matos, C.A. et al. (2018). Gene Therapies for Polyglutamine Diseases. In: Nóbrega, C., Pereira de Almeida, L. (eds) Polyglutamine Disorders. Advances in Experimental Medicine and Biology, vol 1049. Springer, Cham. https://doi.org/10.1007/978-3-319-71779-1_20

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