BACKGROUND: Neovascular, or wet, age-related @entity1020 causes central @entity1018 and represents a major health problem in elderly @entity1 , and is currently treated with frequent intraocular injections of anti- @entity7 protein. Gene therapy might enable long-term anti- @entity7 therapy from a single treatment. We tested the safety of rAAV.sFLT-1 in treatment of wet age-related @entity1020 with a single subretinal injection. METHODS: In this single-centre, phase 1, randomised controlled trial, we enrolled @entity1 with wet age-related @entity1020 at the Lions Eye Institute and the Sir Charles Gairdner Hospital (Nedlands, WA, Australia). Eligible @entity1 had to be aged 65 years or older, have age-related @entity1020 secondary to active subfoveal @entity3193 , with best corrected visual acuity (BCVA) of 3/60-6/24 and 6/60 or better in the other eye. @entity1 were randomly assigned (3:1) to receive either 1   *   10(10) vector genomes (vg; low-dose rAAV.sFLT-1 group) or 1   *   10(11) vg (high-dose rAAV.sFLT-1 group), or no gene-therapy treatment (control group). Randomisation was done by sequential group assignment. All @entity1 and investigators were unmasked. Staff doing the assessments were masked to the study group at study visits. All @entity1 received ranibizumab at baseline and week 4, and rescue treatment during follow-up based on prespecified criteria including BCVA measured on the Early Treatment @entity6 Study (EDTRS) scale, optical coherence tomography, and @entity941 angiography. The primary endpoint was ocular and systemic safety. This trial is registered with ClinicalTrials.gov, number NCT01494805. FINDINGS: From Dec 16, 2011, to April 5, 2012, we enrolled nine @entity1 of whom eight were randomly assigned to receive either intervention (three @entity1 in the low-dose rAAV.sFLT-1 group and three @entity1 in the high-dose rAAV.sFLT-1 group) or no treatment (two @entity1 in the control group). Subretinal injection of rAAV.sFLT-1 was highly reproducible. No drug-related adverse events were noted; procedure-related adverse events (subconjunctival or subretinal @entity548 and mild cell debris in the anterior vitreous) were generally mild and self-resolving. There was no evidence of @entity5066 . Clinical laboratory assessments generally remained unchanged from baseline. Four (67%) of six @entity1 in the treatment group required zero rescue injections, and the other two (33%) required only one rescue injection each. INTERPRETATION: rAAV.sFLT-1 was safe and well tolerated. These results support ocular gene therapy as a potential long-term treatment option for wet age-related @entity1020 . FUNDING: National Health and Medical Research Council of Australia, Richard Pearce Bequest, Lions Save Sight Foundation, Brian King Fellowship, and Avalanche Biotechnologies, Inc.

Gene therapy with recombinant adeno-associated vectors for neovascular age-related XXXX : 1 year follow-up of a phase 1 randomised clinical trial.

@entity1018 :: ('MESH:D054062', 'Disease') :: ['vision loss'] @entity1 :: ('9606', 'Species') :: ['Patients', 'patients', 'people'] @entity5066 :: ('MESH:C566236', 'Disease') :: ['chorioretinal atrophy'] @entity6 :: ('MESH:D003920', 'Disease') :: ['Diabetic Retinopathy'] @entity7 :: ('7422', 'Gene') :: ['VEGF'] @entity548 :: ('MESH:D006470', 'Disease') :: ['haemorrhage'] @entity3193 :: ('MESH:D015862', 'Disease') :: ['choroidal neovascularisation'] @entity941 :: ('MESH:D019793', 'Chemical') :: ['fluorescein'] @entity1020 :: ('MESH:D008268', 'Disease') :: ['macular degeneration']
@entity1020 :: (MESH:D008268,Disease) :: ['macular degeneration']
