Safety and Long-Term Efficacy of AAV4 Gene Therapy in Patients with RPE65 Leber Congenital Amaurosis
In: ISSN: 1525-0016, 2018
academicJournal
Zugriff:
International audience ; The aim of this study was the evaluation of the safety and efficacy of unilateral subretinal injection of the adeno-associated vector (AAV) serotypes 2 and 4 (AAV2/4) RPE65-RPE65 vector in patients with Leber congenital amaurosis (LCA) associated with RPE65 gene deficiency. We evaluated ocular and general tolerance and visual function up to 1 year after vector administration in the most severely affected eye in nine patients with retinal degeneration associated with mutations in the RPE65 gene. Patients received either low (1.22 × 1010 to 2 × 1010 vector genomes [vg]) or high (between 3.27 × 1010 and 4.8 × 1010 vg) vector doses. An ancillary study, in which six of the original nine patients participated, extended the follow-up period to 2-3.5 years. All patients showed good ophthalmological and general tolerance to the rAAV2/4-RPE65-RPE65 vector. We observed a trend toward improved visual acuity in patients with nystagmus, stabilization and improvement of the visual field, and cortical activation along visual pathways during fMRI analysis. OCT analysis after vector administration revealed no retinal thinning, except in cases of macular detachment. Our findings show that the rAAV2/4.RPE65.RPE65 vector was well tolerated in nine patients with RPE65-associated LCA. Efficacy parameters varied between patients during follow-up.
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Safety and Long-Term Efficacy of AAV4 Gene Therapy in Patients with RPE65 Leber Congenital Amaurosis
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| Autor/in / Beteiligte Person: | Le Meur, Guylène ; Lebranchu, Pierre ; Billaud, Fanny ; Adjali, Oumeya ; Schmitt, Sébastien ; Bézieau, Stéphane ; Péréon, Yann ; Valabregue, Romain ; Ivan, Catherine ; Darmon, Christophe ; Moullier, Philippe ; Rolling, Fabienne ; Weber, Michel ; Service d'ophtalmologie CHU Nantes ; Centre Hospitalier Universitaire de Nantes = Nantes University Hospital (CHU Nantes) ; Laboratoire de Thérapie Génique Translationnelle des Maladies Génétiques (Inserm UMR 1089) ; Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE) ; Université de Nantes (UN)-Université de Nantes (UN) ; Image Perception Interaction (LS2N - équipe IPI) ; Laboratoire des Sciences du Numérique de Nantes (LS2N) ; Université de Nantes - UFR des Sciences et des Techniques (UN UFR ST) ; Université de Nantes (UN)-Université de Nantes (UN)-École Centrale de Nantes (ECN)-Centre National de la Recherche Scientifique (CNRS)-IMT Atlantique (IMT Atlantique) ; Institut Mines-Télécom Paris (IMT)-Institut Mines-Télécom Paris (IMT)-Université de Nantes - UFR des Sciences et des Techniques (UN UFR ST) ; Institut Mines-Télécom Paris (IMT)-Institut Mines-Télécom Paris (IMT) ; Service de génétique médicale CHU Nantes ; Reference Centre for Neuromuscular Disorders ( FILNEMUS) ; Plateforme de neuroimagerie CENIR = Center for NeuroImaging Research-Human MRI Neuroimaging core facility for clinical research ICM Paris (CENIR) ; Institut du Cerveau = Paris Brain Institute (ICM) ; Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière AP-HP ; Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière AP-HP ; Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS) |
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| Zeitschrift: | ISSN: 1525-0016, 2018 |
| Veröffentlichung: | HAL CCSD ; Cell Press, 2018 |
| Medientyp: | academicJournal |
| DOI: | 10.1016/j.ymthe.2017.09.014 |
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