Safety and efficacy of gene transfer for Leber's congenital amaurosis.
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 DNA (cDNA) (ClinicalTrials.gov number, NCT00516477 [ClinicalTrials.gov]). Three patients with LCA2 had an acceptable local and systemic adverse-event profile after delivery of AAV2.hRPE65v2. Each patient had a modest improvement in measures of retinal function on subjective tests of visual acuity. In one patient, an asymptomatic macular hole developed, and although the occurrence was considered to be an adverse event, the patient had some return of retinal function. Although the follow-up was very short and normal vision was not achieved, this study provides the basis for further gene therapy studies in patients with LCA.
Maguire
Albert M
AM
Scheie Eye Institute, University of Pennsylvania, USA.
Simonelli
Francesca
F
Pierce
Eric A
EA
Pugh
Edward N
EN
Mingozzi
Federico
F
Bennicelli
Jeannette
J
Banfi
Sandro
S
Marshall
Kathleen A
KA
Testa
Francesco
F
Surace
Enrico M
EM
Rossi
Settimio
S
Lyubarsky
Arkady
A
Arruda
Valder R
VR
Konkle
Barbara
B
Stone
Edwin
E
Sun
Junwei
J
Jacobs
Jonathan
J
Dell'Osso
Lou
L
Hertle
Richard
R
Ma
Jian-xing
JX
Redmond
T Michael
TM
Zhu
Xiaosong
X
Hauck
Bernd
B
Zelenaia
Olga
O
Shindler
Kenneth S
KS
Maguire
Maureen G
MG
Wright
J Fraser
JF
Volpe
Nicholas J
NJ
McDonnell
Jennifer Wellman
JW
Auricchio
Alberto
A
High
Katherine A
KA
Bennett
Jean
J
D000328:Adult; D001766:Blindness / Q000151:congenital / Q000235:genetics / Q000473:pathology / Q000628:therapy*; D002352:Carrier Proteins / Q000235:genetics*; D018076:DNA, Complementary; D000229:Dependovirus / Q000235:genetics; D005136:Eye Proteins / Q000235:genetics*; D018014:Gene Transfer Techniques; D015316:Genetic Therapy; D005822:Genetic Vectors; D006801:Humans; D007267:Injections; D009154:Mutation; D011401:Promoter Regions, Genetic; D012025:Reflex, Pupillary; D012160:Retina / Q000473:pathology; D012162:Retinal Degeneration / Q000151:congenital / Q000235:genetics / Q000473:pathology / Q000628:therapy*; D014792:Visual Acuity; D019745:cis-trans-Isomerases; D000099178:Retinoid Isomerohydrolase
D002352:Carrier Proteins; D018076:DNA, Complementary; D005136:Eye Proteins; D019745:cis-trans-Isomerases; D000099178:Retinoid Isomerohydrolase