Gene therapy rescues cone function in congenital achromatopsia

Komaromy, A. M.; Alexander, J. J.; Rowlan, J. S.; Garcia, M. M.; Chiodo, V. A.; Kaya, A.; Tanaka, J. C.; Acland, G. M.; Hauswirth, William W.; Aguirre, Gustavo D.

doi:10.1093/hmg/ddr429

Cited by 23 publications

(33 citation statements)

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“…Researchers have found that the robustness and stability of the observed treatment effect were independent of mutation but dependent on both promoter type and age. Komaromy et al (2010) achieved a stable therapeutic effect (for at least 33 months) in younger animals. Because mutations in the CNGB3 gene are the most prevalent cause of achromatopsia, accounting for more than 50% of all known cases of this disease, this study provides proof-of-concept for a potential therapy to treat the biggest subset of patients.…”

Section: Other Hereditary Retinal Diseases Amenable To Gene-replacemementioning

confidence: 86%

Gene Therapy for Blindness

Sahel

Roska

2013

Annu. Rev. Neurosci.

130

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Sight-restoring therapy for the visually impaired and blind is a major unmet medical need. Ocular gene therapy is a rational choice for restoring vision or preventing the loss of vision because most blinding diseases originate in cellular components of the eye, a compartment that is optimally suited for the delivery of genes, and many of these diseases have a genetic origin or genetic component. In recent years we have witnessed major advances in the field of ocular gene therapy, and proof-of-concept studies are under way to evaluate the safety and efficacy of human gene therapies. Here we discuss the concepts and recent advances in gene therapy in the retina. Our review discusses traditional approaches such as gene replacement and neuroprotection and also new avenues such as optogenetic therapies. We conjecture that advances in gene therapy in the retina will pave the way for gene therapies in other parts of the brain.

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Section: Other Hereditary Retinal Diseases Amenable To Gene-replacemementioning

confidence: 86%

Gene Therapy for Blindness

Sahel

Roska

2013

Annu. Rev. Neurosci.

130

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“…CNG channels open in the dark and close upon light stimulation due to a decreased concentration of cGMP, which allows for further downstream photoreceptor signal transduction. Mouse models (GNAT2, CNGA3, and CNGB3 deficiency), canine models of CNGB3 deficiency, and a sheep model of CNGA3 deficiency have been treated with gene replacement, yielding increased visual function [Alexander et al, ; Komaromy et al, ; Michalakis et al, ; Carvalho et al, ; Pang et al, ; Banin et al, ]. A phase I/II clinical trial sponsored by AGTC in collaboration with the National Eye Institute (NEI) is currently recruiting patients for a safety and efficacy study for AAV‐mediated delivery of CNGB3 to patients with congenital achromatopsia caused by mutations in CNGB3 (NCT02599922).…”

Section: Gene Therapy For Inherited Retinal Disordersmentioning

confidence: 99%

Gene and cell‐based therapies for inherited retinal disorders: An update

Sengillo¹,

Justus²,

Tsai³

et al. 2016

American J of Med Genetics Pt C

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Retinal degenerations present a unique challenge as disease progression is irreversible and the retina has little regenerative potential. No current treatments for inherited retinal disease have the ability to reverse blindness, and current dietary supplement recommendations only delay disease progression with varied results. However, the retina is anatomically accessible and capable of being monitored at high resolution in vivo. This, in addition to the immune-privileged status of the eye, has put ocular disease at the forefront of advances in gene- and cell-based therapies. This review provides an update on gene therapies and randomized control trials for inherited retinal disease, including Leber congenital amaurosis, choroideremia, retinitis pigmentosa, Usher syndrome, X-linked retinoschisis, Leber hereditary optic neuropathy, and achromatopsia. New gene-modifying and cell-based strategies are also discussed. © 2016 Wiley Periodicals, Inc.

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“…Mutations in the genes encoding the phototransduction proteins cone transducin (GNAT2 gene) and phosphodiesterace 6C (PDE6C) have also been found in association with achromatopsia. The most common cause of achromatopsia in humans is mutations in the CNGB3 gene, and a recent study using gene therapy in a canine model of a CNGB3 defect showed rescue of cone photoreceptor function (Komáromy, Alexander, SRowlan, Garcia, Chiodo, Kaya, Tanaka, Acland, Hauswirth & Aguirre, 2010). …”

Section: Genes and Photopigmentsmentioning

confidence: 99%

The genetics of normal and defective color vision

2011

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The contributions of genetics research to the science of normal and defective color vision over the previous few decades are reviewed emphasizing the developments in the 25 years since the last anniversary issue of Vision Research. Understanding of the biology underlying color vision has been vaulted forward through the application of the tools of molecular genetics. For all their complexity, the biological processes responsible for color vision are more accessible than for many other neural systems. This is partly because of the wealth of genetic variations that affect color perception, both within and across species, and because components of the color vision system lend themselves to genetic manipulation. Mutations and rearrangements in the genes encoding the long, middle, and short wavelength sensitive cone pigments are responsible for color vision deficiencies and mutations have been identified that affect the number of cone types, the absorption spectrum of the pigments, the functionality and viability of the cones, and the topography of the cone mosaic. The addition of an opsin gene, as occurred in the evolution of primate color vision, and has been done in experimental animals can produce expanded color vision capacities and this has provided insight into the underlying neural circuitry.

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Gene therapy rescues cone function in congenital achromatopsia

Cited by 23 publications

References 0 publications

Gene Therapy for Blindness

Gene Therapy for Blindness

Gene and cell‐based therapies for inherited retinal disorders: An update

The genetics of normal and defective color vision

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