EURETINA 2024: Subretinal gene therapy improves function and structure in patients with Bothnia Dystrophy
Bothnia Dystrophy generally presents during early childhood; patients have night blindness, progressive visual loss, and subsequent legal blindness.
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Patients with Bothnia Dystrophy, a rare form of retinitis pigmentosa that causes legal blindness by early adulthood, benefited from subretinal administration of AAV8-RLBP1 gene therapy, which was considered safe and well tolerated, according to lead author Anders Kvanta, MD, from St. Erik Eye Hospital, Karolinska Institute, Stockholm, who discussed the findings at the 24th Euretina Congress in Barcelona.
Bothnia Dystrophy generally presents during early childhood; patients have night blindness, progressive visual loss, and subsequent legal blindness.
Kvanta and colleagues conducted an open-label, dose-escalating, first-in-human, phase 1/2 study that included 12 patients with very delayed dark adaptation (DA) who received increasing subretinal AAV8-RLBP1 doses (5x109 to 1 x1011 vg/eye). Ocular and systemic safety; DA kinetics, the primary efficacy endpoint; and other light- and dark-adapted visual function measures were assessed.
Following overnight DA, recovery to full-field stimuli was assessed over 6 hours, Kvanta explained.
DA recovered with short-wavelength stimuli (450 nm) and improved in 8 of 12 patients 1 hour after bleaching light, 11 patients at 2 hours, and 9 patients at 3 hours. The improvements were sustained to the latest follow-up. Patients also reported improvement in daily activities. The prevalence of baseline punctata albescens decreased rapidly with the improved DA parameters in the treated eyes of 3 patients.
Other measures of light- and dark-adapted visual function (best-corrected visual acuity, contrast sensitivity, perimetry, and microperimetry) did not differ significantly.
The higher doses caused intraocular inflammation, which responded to steroids, and localized hyperpigmentation with retinal pigment epithelial atrophy.
AAV8-RLBP1, overall safe and well tolerated, showed long-lasting improvement in DA kinetics and anatomic phenotypes in these patients.
