Among many clinical trials of gene therapy for hereditary retinal diseases, a phase 3 clinical trial of voretigene neparvovec (AAV2-hRPE65v2, Luxturna) recently showed significant efficacy for RPE65-mediated inherited retinal dystrophy including Leber congenital amaurosis and RP.
The blonde fundus in such cases may exhibit phenotypic overlap and shared therapeutic implications with other aggressive chorioretinal dystrophies such as end-stage choroideremia, gyrate atrophy, or RPE65-Leber congenital amaurosis.
Leber congenital amaurosis (LCA) is a severe, genetically heterogeneous dystrophy of the retina and mutations in the nicotinamide mononucleotide adenylyltransferase 1 (NMNAT1) gene is one of causal factors of LCA.
Various blinding conditions in humans, such as Leber congenital amaurosis and retinitis pigmentosa (RP), are attributed to either homozygous or compound heterozygous mutations in RPE65.
In the present study, we assessed the potentially deleterious effects of long-term expression of these optogenes on the diseased retina in a large animal model of retinal degeneration, the RPE65-deficient Briard dog model of Leber congenital amaurosis.
Pathogenic variants in CRB1 lead to a huge variety of phenotypes ranging from milder forms of inherited retinal dystrophy, such as retinitis pigmentosa to more severe phenotypes such as Leber congenital amaurosis.
Leber congenital amaurosis (LCA) is a visual disease which is caused by RPE65 mutations and results in retinal degeneration and severe vision loss in early infancy.
Targeted next generation sequencing identified novel mutations in RPGRIP1 associated with both retinitis pigmentosa and Leber's congenital amaurosis in unrelated Chinese patients.
Efficacy and safety of voretigene neparvovec (AAV2-hRPE65v2) in patients with RPE65-mediated inherited retinal dystrophy: a randomised, controlled, open-label, phase 3 trial.
Mutations in the RPGR-interacting protein 1 (RPGRIP1) gene cause recessive Leber congenital amaurosis (LCA), juvenile retinitis pigmentosa (RP) and cone-rod dystrophy.
These mouse models offer an opportunity for investigating the cellular mechanisms underlying disease pathogenesis, evaluating potential therapies for NMNAT1-Leber congenital amaurosis, and conducting in situ studies on NMNAT1 function and NAD(+) metabolism.
Safety and durability of effect of contralateral-eye administration of AAV2 gene therapy in patients with childhood-onset blindness caused by RPE65 mutations: a follow-on phase 1 trial.