RNA interference-based therapy for spinocerebellar ataxia type 7 retinal degeneration.
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.
Interdisciplinary program in Genetics, University of Iowa, Iowa City, Iowa, United States of America.
Pavitra S
PS
Ramachandran
Department of Ophthalmology and Visual sciences, University of Iowa, Iowa City, Iowa, United States of America.
Sajag
S
Bhattarai
Department of Ophthalmology and Visual sciences, University of Iowa, Iowa City, Iowa, United States of America.
Pratibha
P
Singh
Department of Internal Medicine, University of Iowa, Iowa City, Iowa, United States of America.
Ryan L
RL
Boudreau
Department of Ophthalmology and Visual sciences, University of Iowa, Iowa City, Iowa, United States of America.
Stewart
S
Thompson
Departments of Pediatrics, Cellular & Molecular Medicine, and Neurosciences, Division of Biological Sciences, the Institute for Genomic Medicine, and the Sanford Consortium for Regenerative Medicine, University of California San Diego, La Jolla, California, United States of America.
Albert R
AR
Laspada
Department of Ophthalmology and Visual sciences, University of Iowa, Iowa City, Iowa, United States of America.
Arlene V
AV
Drack
Interdisciplinary program in Genetics, University of Iowa, Iowa City, Iowa, United States of America; Department of Internal Medicine, University of Iowa, Iowa City, Iowa, United States of America; Department of Neurology, University of Iowa, Iowa City, Iowa, United States of America; Department of Physiology and Biophysics, University of Iowa, Iowa City, Iowa, United States of America.
Beverly L
BL
Davidson
D000818:Animals; D000067719:Ataxin-7; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009419:Nerve Tissue Proteins / Q000235:genetics; D034622:RNA Interference / Q000502:physiology*; D012162:Retinal Degeneration / Q000235:genetics / Q000628:therapy*; D020754:Spinocerebellar Ataxias / Q000235:genetics* / Q000628:therapy*
C000593829:ATXN7 protein, human; D000067719:Ataxin-7; C000593831:Atxn7 protein, mouse; D009419:Nerve Tissue Proteins