Gene Therapy for Age-Related Macular Degeneration. Issue 4 (July 2016)

• Record Type: Journal Article
• Authors: Constable, Ian Jeffery; Blumenkranz, Mark Scott; Schwartz, Steven D.; Barone, Sam; Lai, Chooi-May; Rakoczy, Elizabeth Piroska
• Is Part Of: Asia-Pacific journal of ophthalmology. Volume 5:Issue 4(2016)
• Publication Date: 2016-07
• Subjects: macular degeneration -- gene therapy -- adeno-associated virus -- sFlt; Ophthalmology -- Periodicals; Eye -- Diseases -- Periodicals; Periodicals; 617.7005
• DOI: 10.1097/APO.0000000000000222
• Languages: English
• ISSNs: 0129-1653

Abstract

Abstract : Abstract: The purpose of this article was to evaluate safety and signals of efficacy of gene therapy with subretinal rAAV.sFlt-1 for wet age-related macular degeneration (wet AMD). A phase 1 dose-escalating single-center controlled unmasked human clinical trial was followed up by extension of the protocol to a phase 2A single-center trial. rAAV.sFlt-1 vector was used to deliver a naturally occurring anti–vascular endothelial growth factor agent, sFlt-1, into the subretinal space. In phase 1, step 1 randomized 3 subjects to low-dose rAAV.sFlt-1 (1 × 10 10 vector genomes) and 1 subject to the control arm; step 2 randomized an additional 3 subjects to treatment with high-dose rAAV.sFlt-1 (1 × 10 11 vector genomes) and 1 subject to the control arm. Follow-up studies demonstrated that rAAV.sFlt-1 was well tolerated with a favorable safety profile in these elderly subjects with wet AMD. Subretinal injection was highly reproducible, and no drug-related adverse events were reported. Procedure-related adverse events were mild and self-resolving. Two phakic patients developed cataract and underwent cataract surgery. Four of the 6 patients responded better than the small control group in this study and historical controls in terms of maintaining vision and a relatively dry retina with zero ranibizumab retreatments per annum. Two patients required 1 ranibizumab injection over the 52-week follow-up period. rAAV.sFlt-1 gene therapy may prove to be a potential adjunct or alternative to conventional intravitreal injection for patients with wet AMD by providing extended delivery of a naturally occurring antiangiogenic protein.