MeiraGTx Holdings PLC, a clinical stage genetic medicines company, announced the publication of results from its first-in-human interventional study treating children with AIPL1-associated severe retinal dystrophy (Leber Congenital Amaurosis 4 (LCA4)). Appearing in the Lancet, the paper, "Gene therapy in children with AIPL1-associated severe retinal dystrophy: an open-label, first-in-human interventional study," showed that the first 4 children treated unilaterally with rAAV8.hRKp.AIPL1 benefited substantially from unilateral subretinal administration, with improved visual acuity, functional vision, and protection against progressive retinal degeneration.
Following the strong safety and substantial efficacy demonstrated in this first cohort of 4 children treated unilaterally, an additional 7 children were given sequential, bilateral treatment with rAAV8.hRKp.AIPL1 and all showed substantial benefit as well. According to the researchers, all 11 of the 11 children treated, ages 1 to 3 years and who were blind at birth, now have visual acuity in the treated eyes.
The genetic medicine was a recombinant adeno-associated viral vector, comprising the human AIPL1 coding sequence driven by a human rhodopsin kinase promoter region (rAAV8.hRKp.AIPL1), according to a MeiraGTx press release. The product was manufactured under a Specials License from the UK Medicines and Healthcare products Regulatory Authority (MHRA) and made available to affected children with local ethics approval. Outcome measures included visual acuity (as assessed with standard-of-care testing as well as a novel touchscreen test), functional vision (assessed by observing and recording the children’s visual behavior and their ability to perform simple vision-guided tasks), visual evoked potentials (assessed by recording cortical electrophysiological responses to full-screen black-and-white flickering stimuli), and retinal structure (assessed with handheld OCT and widefield fundus imaging).
To see the full study, go to: https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(24)02812-5/fulltext