Gene therapy for inherited retinal dystrophy

What the study found

In a 2017 Lancet phase 3 trial, patients with inherited retinal dystrophy caused by mutations in both copies of the RPE65 gene received voretigene neparvovec, a gene therapy injected under the retina that uses an AAV2 viral vector to deliver a functional RPE65 gene. Compared with untreated controls, treated patients improved on a navigation test through a dimly lit obstacle course — a measure of real-world functional vision — along with gains in light sensitivity.

How it works

RPE65 encodes an enzyme the retina needs to regenerate the light-sensing pigment in photoreceptors; without it, vision fails progressively from childhood. The therapy supplies working copies of the gene directly to retinal cells. The eye is a favorable target for gene therapy: it is small, enclosed, and partly shielded from the immune system, so a locally injected vector stays where it is placed.

Analysis — the pattern

This became one of the first directly administered gene therapies approved for an inherited disease (analysis): it helped establish that AAV-delivered gene replacement could produce a measurable functional benefit, and it reinforced treating early, before photoreceptors are lost. It also modeled how to measure success for vision — a functional navigation task rather than only a standard eye chart.

What is still uncertain

The trial was small and specific to RPE65 mutations, so it does not extend to other causes of inherited blindness. How long the benefit lasts, whether effects fade, and the very high cost remain open questions the field continues to study.