Beneficial effects on vision in patients undergoing retinal gene therapy for choroideremia

Abstract

Retinal gene therapy is increasingly recognised as a novel molecular intervention that has huge potential in treating common causes of blindness, the majority of which have a genetic aetiology. 1-5 Choroideremia is a chronic X-linked retinal degeneration that was first described in 1872. 6 It leads to progressive blindness due to deficiency of Rab-escort protein 1 (REP1). We designed an adenoassociated viral vector to express REP1 and assessed it in a gene therapy clinical trial by subretinal injection in 14 patients with choroideremia. The primary endpoint was vision change in treated eyes two years after surgery compared to unoperated fellow eyes. Despite complications in two patients, visual acuity improved in the 14 treated eyes over controls (median 4.5 letter gain, vs 1.5 letter loss, p=0.04), with six treated eyes gaining more than one line of vision (>5 letters). The results suggest that retinal gene therapy can sustain and improve visual acuity in a cohort of predominantly late stage choroideremia patients in whom rapid visual acuity loss would ordinarily be predicted.

Multimodal imaging of late-onset retinal degeneration complicated by bilateral choroidal neovascularization

“…Within the eye, C1QTNF5 is significantly expressed in the RPE, ciliary process and lens epithelium, with studies showing an important role in adhesion between the RPE and Bruch's membrane [2,3]. Continued research is necessary to further elucidate the function of C1QTNF5 and the pathogenesis of LORD, which could lead to the development of novel treatment strategies, possibly including retinal gene (CRISPR/Cas9) and cell based therapies [4,5,6].…”

The Impact of Progressive Visual Field Constriction on Reading Ability in an Inherited Retinal Degeneration

“…Retinal gene therapy has been shown to help preserve or improve visual acuity in advanced choroideremia [15]. In addition, gene replacement may also improve the retinal sensitivity over the macula, thereby further benefiting reading speed.…”

“…The area of functional retina can be accurately quantified by autofluorescence (AF) imaging and microperimetry, providing information about the effective visual field to allow a real-world understanding of the impact on reading performance [13,14]. This is becoming more important since the development of phase III gene therapy trials for choroideremia, following the successful completion of phase I/II studies [15]. This information can also be applied to other inherited retinal dystrophies, particularly rod-cone dystrophies or conditions causing variable visual field defects affecting the periphery more than the centre.…”

Ophthalmology research in the UK’s National Health Service: the structure and performance of the NIHR’s Ophthalmology research portfolio

“…Given the contribution of these two disease groups, respectively, to vision impairment [10] and ocular morbidity [11], and the substantial commercial interests in these diseases, further commercially funded research development in these areas would be welcome. Ophthalmology remains a leader among other specialties within the UK in terms of research into novel research areas such as gene therapies [12], novel drug delivery systems [13], robotic surgery [14] and artificial intelligence [15], all of which have enormous growth potential.…”