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Leber's congenital amaurosis (LCA) is a group of inherited blinding diseases with onset during childhood. One form of the disease, LCA2, is caused by mutations in the retinal pigment epithelium-specific 65-kDa protein gene (RPE65). We investigated the safety of subretinal delivery of a recombinant adeno-associated virus (AAV) carrying RPE65 complementary(More)
The safety and efficacy of gene therapy for inherited retinal diseases is being tested in humans affected with Leber's congenital amaurosis (LCA), an autosomal recessive blinding disease. Three independent studies have provided evidence that the subretinal administration of adeno-associated viral (AAV) vectors encoding RPE65 in patients affected with LCA2(More)
BACKGROUND Gene therapy has the potential to reverse disease or prevent further deterioration of vision in patients with incurable inherited retinal degeneration. We therefore did a phase 1 trial to assess the effect of gene therapy on retinal and visual function in children and adults with Leber's congenital amaurosis. METHODS We assessed the retinal and(More)
OBJECTIVE The aim of this study was to show the clinical data of long-term (3-year) follow-up of 5 patients affected by Leber congenital amaurosis type 2 (LCA2) treated with a single unilateral injection of adeno-associated virus AAV2-hRPE65v2. DESIGN Clinical trial. PARTICIPANTS Five LCA2 patients with RPE65 gene mutations. METHODS After informed(More)
BACKGROUND Safety and efficacy have been shown in a phase 1 dose-escalation study involving a unilateral subretinal injection of a recombinant adeno-associated virus (AAV) vector containing the RPE65 gene (AAV2-hRPE65v2) in individuals with inherited retinal dystrophy caused by RPE65 mutations. This finding, along with the bilateral nature of the disease(More)
We wanted to examine the longitudinal effects of chronic cigarette smoke exposure, and to determine whether the chronic alterations in pulmonary function induced by long-term cigarette smoke exposure in an animal model could be predicted by initial or early alterations in function. A group of Sprague Dawley rats was exposed to the smoke of 7 cigarettes x(More)
To assess the pulmonary structural and functional effects of smoking cessation, we exposed groups of guinea pigs to cigarette smoke for 4 and 8 mo and included a group of animals in which smoke exposure was stopped at 4 mo (ex-smokers). We found that, compared with control nonsmokers, the smokers at both 4 and 8 mo showed airflow obstruction with(More)
Demonstration of safe and stable reversal of blindness after a single unilateral subretinal injection of a recombinant adeno-associated virus (AAV) carrying the RPE65 gene (AAV2-hRPE65v2) prompted us to determine whether it was possible to obtain additional benefit through a second administration of the AAV vector to the contralateral eye. Readministration(More)
Chronic exposure to cigarette smoke is known to produce pulmonary hypertension in humans and in animal models, but the etiology of this process is controversial. To evaluate whether alterations in the structure of the pulmonary capillary bed or the peribronchiolar arterioles could be correlated with the pulmonary arterial pressure (Ppa), we examined the(More)
Cigarette smoke is known to cause acute increases in airway resistance, but the mechanisms behind this effect are unknown. Lung explants were utilized to examine the constrictive effects of acute cigarette smoke exposure on bronchioles from rats in vitro that had or had not been previously exposed to cigarette smoke in vivo. It was found that smoke induced(More)