Journal article
RNA interference-based therapy for spinocerebellar ataxia type 7 retinal degeneration
PloS one, Vol.9(4), e95362
2014
DOI: 10.1371/journal.pone.0095362
PMCID: PMC3997397
PMID: 24759684
Abstract
Spinocerebellar ataxia type 7 (SCA7) is an autosomal dominant neurodegenerative disease characterized by loss of motor coordination and retinal degeneration with no current therapies in the clinic. The causative mutation is an expanded CAG repeat in the ataxin-7 gene whose mutant protein product causes cerebellar and brainstem degeneration and retinal cone-rod dystrophy. Here, we reduced the expression of both mutant and wildtype ataxin-7 in the SCA7 mouse retina by RNA interference and evaluated retinal function 23 weeks post injection. We observed a preservation of normal retinal function and no adverse toxicity with ≥50% reduction of mutant and wildtype ataxin-7 alleles. These studies address an important safety concern regarding non-allele specific silencing of ataxin-7 for SCA7 retinal therapy.
Details
- Title: Subtitle
- RNA interference-based therapy for spinocerebellar ataxia type 7 retinal degeneration
- Creators
- Pavitra S Ramachandran - Interdisciplinary program in Genetics, University of Iowa, Iowa City, Iowa, United States of AmericaSajag Bhattarai - Department of Ophthalmology and Visual sciences, University of Iowa, Iowa City, Iowa, United States of AmericaPratibha Singh - Department of Ophthalmology and Visual sciences, University of Iowa, Iowa City, Iowa, United States of AmericaRyan L Boudreau - Department of Internal Medicine, University of Iowa, Iowa City, Iowa, United States of AmericaStewart Thompson - Department of Ophthalmology and Visual sciences, University of Iowa, Iowa City, Iowa, United States of AmericaAlbert R Laspada - University of California San DiegoArlene V Drack - Department of Ophthalmology and Visual sciences, University of Iowa, Iowa City, Iowa, United States of AmericaBeverly L Davidson - University of Iowa
- Resource Type
- Journal article
- Publication Details
- PloS one, Vol.9(4), e95362
- DOI
- 10.1371/journal.pone.0095362
- PMID
- 24759684
- PMCID
- PMC3997397
- NLM abbreviation
- PLoS One
- ISSN
- 1932-6203
- eISSN
- 1932-6203
- Publisher
- United States
- Grant note
- R01 HD44093 / NICHD NIH HHS P01 NS50210 / NINDS NIH HHS R21 NS082112 / NINDS NIH HHS T32 HL007121 / NHLBI NIH HHS R01 EY014061 / NEI NIH HHS
- Language
- English
- Date published
- 2014
- Academic Unit
- Dermatology; Stead Family Department of Pediatrics; Iowa Neuroscience Institute; Internal Medicine; Ophthalmology and Visual Sciences
- Record Identifier
- 9983980059202771
Metrics
39 Record Views