Gene supplementation therapy for recessive forms of inherited retinal dystrophies

Abstract

Over the last decade, gene supplementation therapy for inherited retinal degeneration has come of age. Early proof-of-concept studies in animal models of disease showed modest, but genuine improvements in retinal function and/or survival. Further development of the vectors used for gene transfer to the retina has led to better treatment efficacy in a wide variety of animal models, leading in 2008 to the initiation of three clinical trials for Leber congenital amaurosis caused by retinal pigment epithelium 65 deficiency. The results from these trials suggest that the treatment of inherited retinal dystrophy by gene therapy can be safe and effective. Here, we examine the progress of gene supplementation therapy in the retina, and discuss the potential for using gene therapy to treat different forms of inherited retinal degeneration.

Gene Therapy Restores Vision and Delays Degeneration in the CNGB1−/− Mouse Model of Retinitis Pigmentosa

“…With the advent of AAVmediated gene replacement therapy, several groups succeeded in restoration of retinal function in RP animal models [12,13]. In this study we present data on the successful restoration of vision in the CNGB1 knockout mouse model of RP us- ing AAV-mediated gene therapy.…”

A “so cilia” network: cilia proteins start “social” networking

“…Strikingly, adeno-associated virus-mediated therapies allowed the recovery of visual cortex activity, even after long sensory deprivation, making such therapies very effective, even in early-onset syndromes (19). Since then, other genetic mutations causing LCA have been targeted either clinically or preclinically, demonstrating the feasibility of such approaches (20). However, the work of Rachel et al, in this issue of the JCI (3), indicates that some mutations in CEP290 are not simple loss-of-function mutations that could be restored by reexpression of CEP290.…”

Subretinal Injection: A Review on the Novel Route of Therapeutic Delivery for Vitreoretinal Diseases

“…The eye, in particular, is an attractive target for gene therapy for the following reasons: (1) insignificant immune responses will occur, (2) only small amounts of viral vectors might be needed to achieve therapeutic effects, (3) it allows localized treatment without intravenous delivery, and (4) the effects, efficacy, and safety can be easily observed and monitored by noninvasive technologies such as electroretinogram and optic coherence tomography [45,46] . Adeno-associated virus (AAV) is a small, nonpathogenic dependovirus that has shown significant promise for safe and stable expression of a genetic payload in the retina [47] , and it has emerged as the vector of choice for gene delivery to the retina.…”