Optogenetic gene therapy restores light sensitivity in seven of ten blind patients

A trial in the New England Journal of Medicine

The study was published late on Wednesday in the New England Journal of Medicine and was led by Botond Roska of the Institute of Molecular and Clinical Ophthalmology Basel (IOB) and José-Alain Sahel of the University of Pittsburgh. It involved ten blind patients with retinitis pigmentosa, a hereditary disease in which the light-sensitive cells of the retina die off gradually. Rather than repairing the damaged cells, the treatment reprograms another cell type that survives in the retina. Researchers introduced the gene for the light-sensitive protein ChrimsonR into remaining ganglion cells, which can then react to amber light. A camera-equipped pair of glasses converts the surroundings into light signals projected onto the retina, and the brain has to learn to interpret them. The study was a Phase 1 trial whose main priority was assessing safety.

What the ten patients could do

Seven of the ten treated patients became more sensitive to light, and six of them crossed a clinical threshold that had been set beforehand, according to watson.ch. Four of eight tested patients could make out the outlines of small objects such as a matchbox, and the study found that being able to recognise a door could greatly simplify everyday life. Reading and recognising faces remained out of reach. Training played a part, as patients who spent more time learning the new visual signals tended to score better in tests.

We are still a long way from patients being able to read or having the kind of vision we are used to.

Background to the trial and the Nobel prize

Five years ago, a first study of this gene therapy took place in Paris with a single person, who gained his first visual impressions through the treatment. After those initial results, the IOB extended the work, and the first participant from Paris took part again in the new study, which was run as a blind study so the patients remain anonymous. On Monday, Karl Deisseroth, Peter Hegemann and Georg Nagel received the 2026 Nobel Prize in Medicine for optogenetics, days before these results appeared. The IOB was founded in 2017 by the University of Basel, the University Hospital Basel and Novartis.

Safety and the size of the patient group

The study reported that the therapy is safe and well tolerated, with side effects limited to mild to moderate, temporary eye inflammation, according to La Razón. Stylianos Michalakis of Ludwig-Maximilians-Universität München (LMU), who was not involved in the work, commented on the results. The researchers estimate that around 1.5 million people worldwide are affected by the disease, and Michalakis put the number in Germany at up to 40,000. The existing gene therapy Luxturna is approved in Europe, but its treatment costs more than 600,000 euros and helps only people with mutations in the RPE65 gene, which experts say covers less than one percent of RP patients. The optogenetic approach works across mutations, although it does not address every cause of the disease.

The therapy concept enables people with RP in the late stage of the disease to achieve a certain artificial vision, so that they can at least find their way around again.

Next steps

Researchers are now working to improve several elements of the therapy, including the light-sensitive proteins that make cells responsive. Futterknecht said the long-term hope is to restore vision as much as possible, and that patients treated should ideally be able to see again without glasses. He said the study shows the therapy could benefit many blind people, not just a small specific group, because all participants had retinitis pigmentosa even though its origins differ.