Towards Mechanism-based Treatments for Fragile X Syndrome
It has been more than 25 years since the identification of the FMR1 gene and the demonstration of the causative role of CGG-repeat expansion in the disease pathology of fragile X syndrome (FXS), but the underlying mechanisms involved in the expansion mutation and the resulting gene silencing still r...
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| Главные авторы: | , |
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| Формат: | Online |
| Язык: | английский |
| Опубликовано: |
MDPI - Multidisciplinary Digital Publishing Institute
2021
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| Предметы: | |
| Online-ссылка: | 42526 |
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| _version_ | 1869518350588051456 |
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| author | Kumari, Daman Gazy, Inbal |
| author_browse | Gazy, Inbal Kumari, Daman |
| author_facet | Kumari, Daman Gazy, Inbal |
| author_sort | Kumari, Daman |
| collection | Directory of Open Access Books |
| description | It has been more than 25 years since the identification of the FMR1 gene and the demonstration of the causative role of CGG-repeat expansion in the disease pathology of fragile X syndrome (FXS), but the underlying mechanisms involved in the expansion mutation and the resulting gene silencing still remain elusive. Our understanding of the pathways impacted by the loss of FMRP function has grown tremendously, and has opened new avenues for targeted treatments for FXS. However, the failure of recent clinical trials that were based on successful preclinical studies using the Fmr1 knockout mouse model has forced the scientific community to revisit clinical trial design and identify objective outcome measures. There has also been a renewed interest in restoring FMR1 gene expression as a possible treatment approach for FXS. This special issue of Brain Sciences highlights the progress that has been made towards understanding the disease mechanisms and how this has informed the development of treatment strategies that are being explored for FXS. |
| format | Online |
| id | doab-20.500.12854ir-61057 |
| institution | Directory of Open Access Books |
| language | eng |
| publishDate | 2021 |
| publishDateRange | 2021 |
| publishDateSort | 2021 |
| publisher | MDPI - Multidisciplinary Digital Publishing Institute |
| publisherStr | MDPI - Multidisciplinary Digital Publishing Institute |
| record_format | ojs |
| spelling | doab-20.500.12854ir-610572024-04-05T12:32:12Z Towards Mechanism-based Treatments for Fragile X Syndrome Kumari, Daman Gazy, Inbal QH301-705.5 Q1-390 n/a lymphoblast pluripotent stem cells FMR1 Gene editing X chromosome Fmr1 epigenetic gene silencing FMR1 gene Fragile X syndrome 1 repeat instability characteristics that have the greatest impact DNA instability working memory language development mosaicism CRISPR 3 clinical trials autism spectrum disorders Fmr1 KO mouse automated vocal analysis base excision repair (BER) inhibitory control cerebral spinal fluid iPSC drug development targeted treatments molecular biomarkers viral vector avoidance biomarker set-shifting early identification expansion anxiety planning voice of the person mismatch repair (MMR) gene reactivation double-strand break repair (DSBR) newborn screening intellectual disability processing speed voice of the patient fragile X syndrome adeno-associated virus neurodevelopmental disorders histone methylation Non-homologous end-joining (NHEJ) ASD Fxr2 Fragile X-associated Tremor/Ataxia Syndrome 2 Trinucleotide Repeat 4 CGG Repeat Expansion Disease DNA methylation contraction fragile X mental retardation protein RNA:DNA hybrid behavior developmental disorders cognition females FMRP Fragile X Syndrome unstable repeat diseases protein synthesis brain cognitive flexibility treatment development fibroblast PRC2 transcription coupled repair (TCR) best practices attention Fragile X executive function thema EDItEUR::P Mathematics and Science::PS Biology, life sciences It has been more than 25 years since the identification of the FMR1 gene and the demonstration of the causative role of CGG-repeat expansion in the disease pathology of fragile X syndrome (FXS), but the underlying mechanisms involved in the expansion mutation and the resulting gene silencing still remain elusive. Our understanding of the pathways impacted by the loss of FMRP function has grown tremendously, and has opened new avenues for targeted treatments for FXS. However, the failure of recent clinical trials that were based on successful preclinical studies using the Fmr1 knockout mouse model has forced the scientific community to revisit clinical trial design and identify objective outcome measures. There has also been a renewed interest in restoring FMR1 gene expression as a possible treatment approach for FXS. This special issue of Brain Sciences highlights the progress that has been made towards understanding the disease mechanisms and how this has informed the development of treatment strategies that are being explored for FXS. 2021-02-12T06:10:59Z 2021-02-12T06:10:59Z 2019-12-09 11:49:15 2019 book 42526 9783039215065 9783039215058 https://directory.doabooks.org/handle/20.500.12854/61057 eng application/octet-stream Attribution-NonCommercial-NoDerivatives 4.0 International https://mdpi.com/books/pdfview/book/1554 MDPI - Multidisciplinary Digital Publishing Institute 10.3390/books978-3-03921-506-5 10.3390/books978-3-03921-506-5 46cabcaa-dd94-4bfe-87b4-55023c1b36d0 9783039215065 9783039215058 250 open access |
| spellingShingle | QH301-705.5 Q1-390 n/a lymphoblast pluripotent stem cells FMR1 Gene editing X chromosome Fmr1 epigenetic gene silencing FMR1 gene Fragile X syndrome 1 repeat instability characteristics that have the greatest impact DNA instability working memory language development mosaicism CRISPR 3 clinical trials autism spectrum disorders Fmr1 KO mouse automated vocal analysis base excision repair (BER) inhibitory control cerebral spinal fluid iPSC drug development targeted treatments molecular biomarkers viral vector avoidance biomarker set-shifting early identification expansion anxiety planning voice of the person mismatch repair (MMR) gene reactivation double-strand break repair (DSBR) newborn screening intellectual disability processing speed voice of the patient fragile X syndrome adeno-associated virus neurodevelopmental disorders histone methylation Non-homologous end-joining (NHEJ) ASD Fxr2 Fragile X-associated Tremor/Ataxia Syndrome 2 Trinucleotide Repeat 4 CGG Repeat Expansion Disease DNA methylation contraction fragile X mental retardation protein RNA:DNA hybrid behavior developmental disorders cognition females FMRP Fragile X Syndrome unstable repeat diseases protein synthesis brain cognitive flexibility treatment development fibroblast PRC2 transcription coupled repair (TCR) best practices attention Fragile X executive function thema EDItEUR::P Mathematics and Science::PS Biology, life sciences Kumari, Daman Gazy, Inbal Towards Mechanism-based Treatments for Fragile X Syndrome |
| title | Towards Mechanism-based Treatments for Fragile X Syndrome |
| title_full | Towards Mechanism-based Treatments for Fragile X Syndrome |
| title_fullStr | Towards Mechanism-based Treatments for Fragile X Syndrome |
| title_full_unstemmed | Towards Mechanism-based Treatments for Fragile X Syndrome |
| title_short | Towards Mechanism-based Treatments for Fragile X Syndrome |
| title_sort | towards mechanism based treatments for fragile x syndrome |
| topic | QH301-705.5 Q1-390 n/a lymphoblast pluripotent stem cells FMR1 Gene editing X chromosome Fmr1 epigenetic gene silencing FMR1 gene Fragile X syndrome 1 repeat instability characteristics that have the greatest impact DNA instability working memory language development mosaicism CRISPR 3 clinical trials autism spectrum disorders Fmr1 KO mouse automated vocal analysis base excision repair (BER) inhibitory control cerebral spinal fluid iPSC drug development targeted treatments molecular biomarkers viral vector avoidance biomarker set-shifting early identification expansion anxiety planning voice of the person mismatch repair (MMR) gene reactivation double-strand break repair (DSBR) newborn screening intellectual disability processing speed voice of the patient fragile X syndrome adeno-associated virus neurodevelopmental disorders histone methylation Non-homologous end-joining (NHEJ) ASD Fxr2 Fragile X-associated Tremor/Ataxia Syndrome 2 Trinucleotide Repeat 4 CGG Repeat Expansion Disease DNA methylation contraction fragile X mental retardation protein RNA:DNA hybrid behavior developmental disorders cognition females FMRP Fragile X Syndrome unstable repeat diseases protein synthesis brain cognitive flexibility treatment development fibroblast PRC2 transcription coupled repair (TCR) best practices attention Fragile X executive function thema EDItEUR::P Mathematics and Science::PS Biology, life sciences |
| topic_facet | QH301-705.5 Q1-390 n/a lymphoblast pluripotent stem cells FMR1 Gene editing X chromosome Fmr1 epigenetic gene silencing FMR1 gene Fragile X syndrome 1 repeat instability characteristics that have the greatest impact DNA instability working memory language development mosaicism CRISPR 3 clinical trials autism spectrum disorders Fmr1 KO mouse automated vocal analysis base excision repair (BER) inhibitory control cerebral spinal fluid iPSC drug development targeted treatments molecular biomarkers viral vector avoidance biomarker set-shifting early identification expansion anxiety planning voice of the person mismatch repair (MMR) gene reactivation double-strand break repair (DSBR) newborn screening intellectual disability processing speed voice of the patient fragile X syndrome adeno-associated virus neurodevelopmental disorders histone methylation Non-homologous end-joining (NHEJ) ASD Fxr2 Fragile X-associated Tremor/Ataxia Syndrome 2 Trinucleotide Repeat 4 CGG Repeat Expansion Disease DNA methylation contraction fragile X mental retardation protein RNA:DNA hybrid behavior developmental disorders cognition females FMRP Fragile X Syndrome unstable repeat diseases protein synthesis brain cognitive flexibility treatment development fibroblast PRC2 transcription coupled repair (TCR) best practices attention Fragile X executive function thema EDItEUR::P Mathematics and Science::PS Biology, life sciences |
| url | 42526 |
| work_keys_str_mv | AT kumaridaman towardsmechanismbasedtreatmentsforfragilexsyndrome AT gazyinbal towardsmechanismbasedtreatmentsforfragilexsyndrome |