Two-Year Results After AAV2-Mediated Gene Therapy for Choroideremia: The Alberta Experience.
Am J Ophthalmol
; 193: 130-142, 2018 09.
Article
em En
| MEDLINE
| ID: mdl-29940166
ABSTRACT
PURPOSE:
To assess the safety of a recombinant adeno-associated viral vector expressing REP1 (rAAV2.REP1) in choroideremia subjects.METHODS:
Design:
Phase I clinical trial.PARTICIPANTS:
Six adult male subjects, 30-42 years of age, with genetically confirmed choroideremia (CHM) were enrolled. The eye with the worse vision, for all subjects, received a single subfoveal injection of 0.1 mL rAAV2.REP1 containing 1011 genome particles. Subjects were followed up for 2 years thereafter. OUTCOMEMEASURES:
The primary outcome measure was safety, determined by the number of ocular and systemic adverse events assessed by ophthalmic examination, spectral-domain optical coherence tomography (SD-OCT), and short-wavelength autofluorescence (FAF). Secondary outcome measures were the change from baseline in best-corrected visual acuity (BCVA) in the treated eye compared to the untreated eye, changes in visual function using microperimetry, and the area of retinal pigment epithelium (RPE) preservation by FAF.RESULTS:
One subject had an 8-ETDRS-letter BCVA loss from baseline measured at 24 months, while 1 subject had a ≥15-letter BCVA gain. A similar improvement was noted in the untreated eye of another subject throughout the follow-up period. Microperimetry sensitivity showed no improvement or significant change up to 2 years after vector administration. The area of preserved RPE as measured by FAF was noted to decline at a similar rate between the treated and untreated eyes. One subject experienced a serious adverse event a localized intraretinal immune response, resulting in marked decline in visual function and loss of SD-OCT outer retinal structures.CONCLUSIONS:
One serious adverse event was experienced in 6 subjects treated with a subfoveal injection of AAV2.REP1. The area of remaining functional RPE in the treated eye and untreated eye declined at the same rate over a 2-year period. Fundus autofluorescence area is a remarkably predictive biomarker and objective outcome measure for future studies of ocular gene therapy in CHM subjects.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Terapia Genética
/
Coroideremia
/
Parvovirinae
/
Proteínas Adaptadoras de Transdução de Sinal
/
Vetores Genéticos
Tipo de estudo:
Clinical_trials
/
Observational_studies
/
Prognostic_studies
/
Risk_factors_studies
Limite:
Adult
/
Humans
/
Male
País/Região como assunto:
America do norte
Idioma:
En
Revista:
Am J Ophthalmol
Ano de publicação:
2018
Tipo de documento:
Article
País de afiliação:
Canadá