Optogenetic gene therapy raises light sensitivity in 7 of 10 retinitis pigmentosa patients

This is the first time the approach has worked across a group rather than in one patient. It does not restore normal sight. No country has approved the therapy.

What the trial measured

Light sensitivity rose in 7 of 10 participants, by a factor of 2.0 to 62.3. Six reached the clinically meaningful threshold, roughly a fourfold gain.

Four of the eight patients who completed behavioral tests got better at detecting or locating objects. Brain activity recordings showed signals consistent with visual information reaching the visual cortex. Patients still could not read or recognize faces.

How the treatment works

Retinitis pigmentosa is an inherited disease. Mutations in more than 100 different genes can cause it, which makes gene-by-gene fixes hard to scale. Instead of repairing photoreceptors, each participant received one injection of an adeno-associated virus vector into the worse-seeing eye. The vector carries the gene for ChrimsonR, a light-sensitive protein, into retinal ganglion cells, which often survive even in advanced disease.

ChrimsonR responds to amber light. Camera goggles capture the scene, a processor turns changes in it into pulses of amber light, and those pulses activate the treated cells. Optogenetics avoids brain surgery and works regardless of which gene caused the disease.

The approach needs a working optic nerve, so it cannot help when damage affects the retina-brain connection. José-Alain Sahel of the University of Pittsburgh and Botond Roska of the Institute of Molecular and Clinical Ophthalmology Basel (IOB) led the study, with funding from French biotech GenSight Biologics.

Safety results

The open-label PIONEER study (NCT03326336) was mainly designed to test safety. Nine of the 10 participants had a total of 34 eye-related adverse events: 23 mild, 10 moderate and one severe. The severe event was a temporary blockage of the central retinal artery right after injection. It cleared within minutes after eye drops.

Earlier case

The result builds on a 2021 case. One man who received the same method could see and count objects.

What happens next

The IOB press release notes that people who spent more time training with the goggles tended to do better, which suggests rehabilitation will be part of any future treatment.

The optogenetic therapy remains experimental. The authors say larger trials must confirm the treatment is safe and effective. For now, the published evidence rests on 10 people.