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Guylene Le Meur, Pierre Lebranchu, Yann Péréon, Sebastien Schmitt, Stéphane Bézieau, Philippe Moullier, Fabienne Rolling, Michel Weber; Gene therapy in Leber congenital amaurosis due to rpe mutations: results of the first six patients included in a clinical trial. Invest. Ophthalmol. Vis. Sci. 2013;54(15):5969.
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© ARVO (1962-2015); The Authors (2016-present)
To present the preliminary data of an AAV4 gene therapy clinical trial in patients with rpe65 retinal degeneration
A phase I/II clinical trial assessed the safety and the efficiency of a subretinal injection with AAV2/4.rpe65.hrep65 vector in the worse eye of patient with rpe65-/- retinal dystrophy. We report the result of the first six treated patients. The first three patients received up to 400 µL and the three following patients up to 800 µL of a vector solution at 6.1010 vector genome/mL. The primary safety endpoints are evaluated by biomicroscopy, laser flare meter, fundus photography, fluorescein angiography, OCT and a tolerance questionnaire. Secondary efficacy endpoints are evaluated by global ERG, multifocal ERG, visual field, near and far visual acuity, color vision test, pupillometry, microperimetry, visual mobility test, functional MRI and fundus autofluorescence.
Patients, 20 to 42 years old, were treated between october 2011 and september 2012. The injected volume was between 200 μL and 770 μL of the vector solution. No adverse effects or ocular inflammation are noticed one year to 2 months after subretinal injection. EDTRS score change on average of 5,8 letters after subretinal injection (0,15 Log MAR). A decrease of the nystagmus is noticed in all patients. A decrease of the moving time in the mobility test in scotopic brightness is found with the treated eye. Visual field modifications in the subretinal area are noticed in patients.
The preliminary data of this AAV4 gene therapy clinical trial in patients with rpe65 retinal degeneration suggested a good tolerance and a functional efficency. This results may be confirmed by the pursuit of the follow up of the first six patients and by the data analysis of next included three patients.
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