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Successful Gene Therapy in the RPGRIP1-deficient Dog: a Large Model of Cone-Rod Dystrophy.

Abstract : For the development of new therapies, proof-of-concept studies in large animal models that share clinical features with their human counterparts represent a pivotal step. For inherited retinal dystrophies primarily involving photoreceptor cells, the efficacy of gene therapy has been demonstrated in canine models of stationary cone dystrophies and progressive rod-cone dystrophies but not in large models of progressive cone-rod dystrophies, another important cause of blindness. To address the last issue, we evaluated gene therapy in the retinitis pigmentosa GTPase regulator interacting protein 1 (RPGRIP1)-deficient dog, a model exhibiting a severe cone-rod dystrophy similar to that seen in humans. Subretinal injection of AAV5 (n = 5) or AAV8 (n = 2) encoding the canine Rpgrip1 improved photoreceptor survival in transduced areas of treated retinas. Cone function was significantly and stably rescued in all treated eyes (18-72% of those recorded in normal eyes) up to 24 months postinjection. Rod function was also preserved (22-29% of baseline function) in four of the five treated dogs up to 24 months postinjection. No detectable rod function remained in untreated contralateral eyes. More importantly, treatment preserved bright- and dim-light vision. Efficacy of gene therapy in this large animal model of cone-rod dystrophy provides great promise for human treatment.
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Contributor : Morgane Le Corre Connect in order to contact the contributor
Submitted on : Monday, March 10, 2014 - 11:10:10 AM
Last modification on : Wednesday, April 27, 2022 - 4:25:39 AM

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Elsa Lhériteau, Lolita Petit, Michel Weber, Guylène Le Meur, Jack-Yves Deschamps, et al.. Successful Gene Therapy in the RPGRIP1-deficient Dog: a Large Model of Cone-Rod Dystrophy.. Molecular Therapy, Cell Press, 2014, 22 (2), pp.265-77. ⟨10.1038/mt.2013.232⟩. ⟨hal-00957330⟩



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