Gene therapy to treat inherited and complex retinal degenerative diseases

  title={Gene therapy to treat inherited and complex retinal degenerative diseases},
  author={Tonia S. Rex},
  journal={Molecular Therapy. Methods \& Clinical Development},
  • T. Rex
  • Published 5 August 2015
  • Biology
  • Molecular Therapy. Methods & Clinical Development
These are exciting times in the field of retinal gene therapy, as impressive successes have been achieved by recombinant adeno-associated viral (rAAV) gene delivery of Rpe65 or Rep1 to the retinal pigment epithelium of patients with Lebers congential amaurosis or choroideremia, respectively.1–5 Instead of being left with incurable blindness, patients are reporting restoration of vision. An advantage of these disease targets is that the affected cell type, the retinal pigment epithelium, is… 
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Human retinal gene therapy for Leber congenital amaurosis shows advancing retinal degeneration despite enduring visual improvement

It is shown that gene therapy improves vision for at least 3 y, but photoreceptor degeneration progresses unabated in humans, and in the canine model, the same result occurs when treatment is at the disease stage equivalent to humans.

Gene replacement therapy in the retinal degeneration slow (rds) mouse: the effect on retinal degeneration following partial transduction of the retina.

It is demonstrated that the potential for ultrastructural improvement is dependent upon the age at which animals are treated, but the effect of a single injection on photoreceptor ultrastructure may be long-term, and that transgene over-expression is of significance.

Gene therapy restores vision and delays degeneration in the CNGB1(-/-) mouse model of retinitis pigmentosa.

Treated CNGB1(-/-) mice performed significantly better than untreated mice in a rod-dependent vision-guided behavior test and hold promise for the treatment of rod channelopathy-associated retinitis pigmentosa by AAV-mediated gene replacement.

XIAP Protection of Photoreceptors in Animal Models of Retinitis Pigmentosa

The results show that XIAP gene therapy provides long-term neuroprotection of photoreceptors at both structural and functional levels, and holds great promise for the treatment of RP.

Gene therapy restores vision and delays degeneration in the CNGB1(-/-) mouse model of retinitis pigmentosa.

The treatment not only led to expression of full-length CNGB1a, but also restored normal levels of the previously degraded CNGA1 subunit of the rod CNG channel, leading to significant morphological preservation and a delay of retinal degeneration.

Effect of gene therapy on visual function in Leber's congenital amaurosis.

Three young adult patients with early-onset, severe retinal dystrophy were administered subretinal injections of recombinant adeno-associated virus vector 2/2 expressing RPE65 complementary DNA (cDNA) under the control of a human R PE65 promoter.

AAV mediated GDNF secretion from retinal glia slows down retinal degeneration in a rat model of retinitis pigmentosa.

This ShH10-mediated glial-derived neurotrophic factor secretion from glia following intravitreal vector administration is a safe and effective means to slow the progression of retinal degeneration in a rat model of retinitis pigmentosa (RP) and shows significant promise as a gene therapy to treat human retina degenerations.

Gene Therapy for Leber's Congenital Amaurosis is Safe and Effective Through 1.5 Years After Vector Administration

The safety of the intervention and the stability of the improvement in visual and retinal function in these subjects support the use of AAV-mediated gene augmentation therapy for treatment of inherited retinal diseases.

AAV-mediated delivery of ciliary neurotrophic factor prolongs photoreceptor survival in the rhodopsin knockout mouse.

Retinitis pigmentosa (RP), an inherited retinal degenerative disease causing blindness, is characterized by progressive apoptotic death of photoreceptors. Therapeutic modification of photoreceptor