Gene therapies for polyglutamine diseases

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

*Corresponding author for this work

Research output: Chapter in Book/Report/Conference proceedingChapterpeer-review

13 Citations (Scopus)


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.
Original languageEnglish
Title of host publicationAdvances in experimental medicine and biology
PublisherSpringer New York LLC
Number of pages44
Publication statusPublished - 2018
Externally publishedYes

Publication series

NameAdvances in Experimental Medicine and Biology
ISSN (Print)0065-2598
ISSN (Electronic)2214-8019


  • Gene silencing
  • Gene therapy
  • Polyglutamine diseases
  • RNA interference
  • Viral and non-viral vectors


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