title: The human visual cortex responds to gene therapy-mediated recovery of retinal function.
abstract: Leber congenital amaurosis (LCA) is a rare degenerative eye disease, linked to mutations in at least 14 genes. A recent gene therapy trial in patients with LCA2, who have mutations in RPE65, demonstrated that subretinal injection of an adeno-associated virus (AAV) carrying the normal cDNA of that gene (AAV2-hRPE65v2) could markedly improve vision. However, it remains unclear how the visual cortex responds to recovery of retinal function after prolonged sensory deprivation. Here, 3 of the gene therapy trial subjects, treated at ages 8, 9, and 35 years, underwent functional MRI within 2 years of unilateral injection of AAV2-hRPE65v2. All subjects showed increased cortical activation in response to high- and medium-contrast stimuli after exposure to the treated compared with the untreated eye. Furthermore, we observed a correlation between the visual field maps and the distribution of cortical activations for the treated eyes. These data suggest that despite severe and long-term visual impairment, treated LCA2 patients have intact and responsive visual pathways. In addition, these data suggest that gene therapy resulted in not only sustained and improved visual ability, but also enhanced contrast sensitivity.
authors: Diffusion Tensor Image Analyses and Brain Morphometry Center, Department of Radiology, Children's Hospital of Philadelphia (CHOP), Philadelphia, Pennsylvania 19104, USA. ashtari@email.chop.edu
authors: Manzar
authors: M
authors: Ashtari
authors: Laura L
authors: LL
authors: Cyckowski
authors: Justin F
authors: JF
authors: Monroe
authors: Kathleen A
authors: KA
authors: Marshall
authors: Daniel C
authors: DC
authors: Chung
authors: Alberto
authors: A
authors: Auricchio
authors: Francesca
authors: F
authors: Simonelli
authors: Bart P
authors: BP
authors: Leroy
authors: Albert M
authors: AM
authors: Maguire
authors: Kenneth S
authors: KS
authors: Shindler
authors: Jean
authors: J
authors: Bennett
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