Reduction of retinal ganglion cell death in mouse models of familial dysautonomia using AAV-mediated gene therapy and splicing modulators
© 2023. The Author(s)..
Familial dysautonomia (FD) is a rare neurodevelopmental and neurodegenerative disease caused by a splicing mutation in the Elongator Acetyltransferase Complex Subunit 1 (ELP1) gene. The reduction in ELP1 mRNA and protein leads to the death of retinal ganglion cells (RGCs) and visual impairment in all FD patients. Currently patient symptoms are managed, but there is no treatment for the disease. We sought to test the hypothesis that restoring levels of Elp1 would thwart the death of RGCs in FD. To this end, we tested the effectiveness of two therapeutic strategies for rescuing RGCs. Here we provide proof-of-concept data that gene replacement therapy and small molecule splicing modifiers effectively reduce the death of RGCs in mouse models for FD and provide pre-clinical foundational data for translation to FD patients.
| Errataetall: | |
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| Medienart: |
E-Artikel |
| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:13 |
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| Enthalten in: |
Scientific reports - 13(2023), 1 vom: 30. Okt., Seite 18600 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Schultz, Anastasia [VerfasserIn] |
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| Links: |
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| Themen: |
Journal Article |
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| Anmerkungen: |
Date Completed 01.11.2023 Date Revised 22.02.2024 published: Electronic UpdateOf: bioRxiv. 2023 May 24;:. - PMID 37293016 Citation Status MEDLINE |
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| doi: |
10.1038/s41598-023-45376-w |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM363958207 |
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| 500 | |a UpdateOf: bioRxiv. 2023 May 24;:. - PMID 37293016 | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a © 2023. The Author(s). | ||
| 520 | |a Familial dysautonomia (FD) is a rare neurodevelopmental and neurodegenerative disease caused by a splicing mutation in the Elongator Acetyltransferase Complex Subunit 1 (ELP1) gene. The reduction in ELP1 mRNA and protein leads to the death of retinal ganglion cells (RGCs) and visual impairment in all FD patients. Currently patient symptoms are managed, but there is no treatment for the disease. We sought to test the hypothesis that restoring levels of Elp1 would thwart the death of RGCs in FD. To this end, we tested the effectiveness of two therapeutic strategies for rescuing RGCs. Here we provide proof-of-concept data that gene replacement therapy and small molecule splicing modifiers effectively reduce the death of RGCs in mouse models for FD and provide pre-clinical foundational data for translation to FD patients | ||
| 650 | 4 | |a Journal Article | |
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| 700 | 1 | |a Cheng, Shun-Yun |e verfasserin |4 aut | |
| 700 | 1 | |a Kirchner, Emily |e verfasserin |4 aut | |
| 700 | 1 | |a Costello, Stephanann |e verfasserin |4 aut | |
| 700 | 1 | |a Miettinen, Heini |e verfasserin |4 aut | |
| 700 | 1 | |a Chaverra, Marta |e verfasserin |4 aut | |
| 700 | 1 | |a King, Colin |e verfasserin |4 aut | |
| 700 | 1 | |a George, Lynn |e verfasserin |4 aut | |
| 700 | 1 | |a Zhao, Xin |e verfasserin |4 aut | |
| 700 | 1 | |a Narasimhan, Jana |e verfasserin |4 aut | |
| 700 | 1 | |a Weetall, Marla |e verfasserin |4 aut | |
| 700 | 1 | |a Slaugenhaupt, Susan |e verfasserin |4 aut | |
| 700 | 1 | |a Morini, Elisabetta |e verfasserin |4 aut | |
| 700 | 1 | |a Punzo, Claudio |e verfasserin |4 aut | |
| 700 | 1 | |a Lefcort, Frances |e verfasserin |4 aut | |
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