Development of LNA gapmer oligonucleotide-based therapy for ALS/FTD caused by the C9orf72 repeat expansion

Several neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS), have a complex genetic background, in addition to cases where the disease appears to manifest sporadically. The recent discovery of the hexanucleotide repeat expansion in the C9orf72 gene as the causative agent of ALS...

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Main Authors: Sathyaprakash, C, Manzano, R, Varela, MA, Hashimoto, Y, Wood, MJA, Talbot, K, Aoki, Y
Format: Journal article
Language:English
Published: Humana Press 2020
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author Sathyaprakash, C
Manzano, R
Varela, MA
Hashimoto, Y
Wood, MJA
Talbot, K
Aoki, Y
author_facet Sathyaprakash, C
Manzano, R
Varela, MA
Hashimoto, Y
Wood, MJA
Talbot, K
Aoki, Y
author_sort Sathyaprakash, C
collection OXFORD
description Several neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS), have a complex genetic background, in addition to cases where the disease appears to manifest sporadically. The recent discovery of the hexanucleotide repeat expansion in the C9orf72 gene as the causative agent of ALS (C9ALS) gives rise to the opportunity to develop new therapies directed at this mutation, which is responsible for a large proportion of ALS and/or frontotemporal dementia cases. Mammalian models conscientiously replicating the late-onset motor defects and cellular pathologies seen in human patients do not exist. In this context, patient-derived cells give us a platform to test potential antisense oligonucleotide therapies, which could be the key to treat this subtype of motor neuron disease. Recently, we described that locked nucleic acid gapmer oligonucleotide-based treatment targeting C9orf72 repeat expanded transcripts resulted in recovery from the disease-related phenotypes in patient-derived fibroblasts. Our findings highlight the therapeutic potential of C9ALS using this gapmer oligonucleotide-based approach.
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spelling oxford-uuid:95959bf6-b06c-4412-925b-3413864ba6e92022-03-26T23:47:04ZDevelopment of LNA gapmer oligonucleotide-based therapy for ALS/FTD caused by the C9orf72 repeat expansionJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:95959bf6-b06c-4412-925b-3413864ba6e9EnglishSymplectic ElementsHumana Press2020Sathyaprakash, CManzano, RVarela, MAHashimoto, YWood, MJATalbot, KAoki, YSeveral neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS), have a complex genetic background, in addition to cases where the disease appears to manifest sporadically. The recent discovery of the hexanucleotide repeat expansion in the C9orf72 gene as the causative agent of ALS (C9ALS) gives rise to the opportunity to develop new therapies directed at this mutation, which is responsible for a large proportion of ALS and/or frontotemporal dementia cases. Mammalian models conscientiously replicating the late-onset motor defects and cellular pathologies seen in human patients do not exist. In this context, patient-derived cells give us a platform to test potential antisense oligonucleotide therapies, which could be the key to treat this subtype of motor neuron disease. Recently, we described that locked nucleic acid gapmer oligonucleotide-based treatment targeting C9orf72 repeat expanded transcripts resulted in recovery from the disease-related phenotypes in patient-derived fibroblasts. Our findings highlight the therapeutic potential of C9ALS using this gapmer oligonucleotide-based approach.
spellingShingle Sathyaprakash, C
Manzano, R
Varela, MA
Hashimoto, Y
Wood, MJA
Talbot, K
Aoki, Y
Development of LNA gapmer oligonucleotide-based therapy for ALS/FTD caused by the C9orf72 repeat expansion
title Development of LNA gapmer oligonucleotide-based therapy for ALS/FTD caused by the C9orf72 repeat expansion
title_full Development of LNA gapmer oligonucleotide-based therapy for ALS/FTD caused by the C9orf72 repeat expansion
title_fullStr Development of LNA gapmer oligonucleotide-based therapy for ALS/FTD caused by the C9orf72 repeat expansion
title_full_unstemmed Development of LNA gapmer oligonucleotide-based therapy for ALS/FTD caused by the C9orf72 repeat expansion
title_short Development of LNA gapmer oligonucleotide-based therapy for ALS/FTD caused by the C9orf72 repeat expansion
title_sort development of lna gapmer oligonucleotide based therapy for als ftd caused by the c9orf72 repeat expansion
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