Oligonucleotide-Based Therapy for FTD/ALS Caused by the C9orf72 Repeat Expansion: A Perspective
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, l...
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| Format: | Article |
| Language: | English |
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Wiley
2013-01-01
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| Series: | Journal of Nucleic Acids |
| Online Access: | http://dx.doi.org/10.1155/2013/208245 |
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| author | Stephanie A. Fernandes Andrew G. L. Douglas Miguel A. Varela Matthew J. A. Wood Yoshitsugu Aoki |
| author_facet | Stephanie A. Fernandes Andrew G. L. Douglas Miguel A. Varela Matthew J. A. Wood Yoshitsugu Aoki |
| author_sort | Stephanie A. Fernandes |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-7fcb91be1c61498a81e76869cb59b180 |
| institution | Kabale University |
| issn | 2090-0201 2090-021X |
| language | English |
| publishDate | 2013-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Journal of Nucleic Acids |
| spelling | doaj-art-7fcb91be1c61498a81e76869cb59b1802025-02-03T01:27:45ZengWileyJournal of Nucleic Acids2090-02012090-021X2013-01-01201310.1155/2013/208245208245Oligonucleotide-Based Therapy for FTD/ALS Caused by the C9orf72 Repeat Expansion: A PerspectiveStephanie A. Fernandes0Andrew G. L. Douglas1Miguel A. Varela2Matthew J. A. Wood3Yoshitsugu Aoki4Department of Physiology, Anatomy and Genetics, University of Oxford, South Parks Road, Oxford OX1 3QX, UKDepartment of Physiology, Anatomy and Genetics, University of Oxford, South Parks Road, Oxford OX1 3QX, UKDepartment of Physiology, Anatomy and Genetics, University of Oxford, South Parks Road, Oxford OX1 3QX, UKDepartment of Physiology, Anatomy and Genetics, University of Oxford, South Parks Road, Oxford OX1 3QX, UKDepartment of Physiology, Anatomy and Genetics, University of Oxford, South Parks Road, Oxford OX1 3QX, UKAmyotrophic 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.http://dx.doi.org/10.1155/2013/208245 |
| spellingShingle | Stephanie A. Fernandes Andrew G. L. Douglas Miguel A. Varela Matthew J. A. Wood Yoshitsugu Aoki Oligonucleotide-Based Therapy for FTD/ALS Caused by the C9orf72 Repeat Expansion: A Perspective Journal of Nucleic Acids |
| title | Oligonucleotide-Based Therapy for FTD/ALS Caused by the C9orf72 Repeat Expansion: A Perspective |
| title_full | Oligonucleotide-Based Therapy for FTD/ALS Caused by the C9orf72 Repeat Expansion: A Perspective |
| title_fullStr | Oligonucleotide-Based Therapy for FTD/ALS Caused by the C9orf72 Repeat Expansion: A Perspective |
| title_full_unstemmed | Oligonucleotide-Based Therapy for FTD/ALS Caused by the C9orf72 Repeat Expansion: A Perspective |
| title_short | Oligonucleotide-Based Therapy for FTD/ALS Caused by the C9orf72 Repeat Expansion: A Perspective |
| title_sort | oligonucleotide based therapy for ftd als caused by the c9orf72 repeat expansion a perspective |
| url | http://dx.doi.org/10.1155/2013/208245 |
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