Oligonucleotide-Based Therapy for FTDALS Caused by the C9orf72 Repeat Expansion : A Perspective
Joint Authors
Varela, Miguel A.
Wood, Matthew J. A.
Douglas, Andrew G. L.
Fernandes, Stephanie A.
Aoki, Yoshitsugu
Source
Issue
Vol. 2013, Issue 2013 (31 Dec. 2013), pp.1-11, 11 p.
Publisher
Hindawi Publishing Corporation
Publication Date
2013-11-17
Country of Publication
Egypt
No. of Pages
11
Main Subjects
Abstract EN
Amyotrophic lateral sclerosis (ALS) is a progressive and lethal disease of motor neuron degeneration, leading to paralysis of voluntary muscles and death by respiratory failure within five years of onset.
Frontotemporal dementia (FTD) is characterised by degeneration of frontal and temporal lobes, leading to changes in personality, behaviour, and language, culminating in death within 5–10 years.
Both of these diseases form a clinical, pathological, and genetic continuum of diseases, and this link has become clearer recently with the discovery of a hexanucleotide repeat expansion in the C9orf72 gene that causes the FTD/ALS spectrum, that is, c9FTD/ALS.
Two basic mechanisms have been proposed as being potentially responsible for c9FTD/ALS: loss-of-function of the protein encoded by this gene (associated with aberrant DNA methylation) and gain of function through the formation of RNA foci or protein aggregates.
These diseases currently lack any cure or effective treatment.
Antisense oligonucleotides (ASOs) are modified nucleic acids that are able to silence targeted mRNAs or perform splice modulation, and the fact that they have proved efficient in repeat expansion diseases including myotonic dystrophy type 1 makes them ideal candidates for c9FTD/ALS therapy.
Here, we discuss potential mechanisms and challenges for developing oligonucleotide-based therapy for c9FTD/ALS.
American Psychological Association (APA)
Fernandes, Stephanie A.& Douglas, Andrew G. L.& Varela, Miguel A.& Wood, Matthew J. A.& Aoki, Yoshitsugu. 2013. Oligonucleotide-Based Therapy for FTDALS Caused by the C9orf72 Repeat Expansion : A Perspective. Journal of Nucleic Acids،Vol. 2013, no. 2013, pp.1-11.
https://search.emarefa.net/detail/BIM-454633
Modern Language Association (MLA)
Fernandes, Stephanie A.…[et al.]. Oligonucleotide-Based Therapy for FTDALS Caused by the C9orf72 Repeat Expansion : A Perspective. Journal of Nucleic Acids No. 2013 (2013), pp.1-11.
https://search.emarefa.net/detail/BIM-454633
American Medical Association (AMA)
Fernandes, Stephanie A.& Douglas, Andrew G. L.& Varela, Miguel A.& Wood, Matthew J. A.& Aoki, Yoshitsugu. Oligonucleotide-Based Therapy for FTDALS Caused by the C9orf72 Repeat Expansion : A Perspective. Journal of Nucleic Acids. 2013. Vol. 2013, no. 2013, pp.1-11.
https://search.emarefa.net/detail/BIM-454633
Data Type
Journal Articles
Language
English
Notes
Includes bibliographical references
Record ID
BIM-454633