Retinitis Pigmentosa Gene Therapy Helps 7 of 10 Blind Patients

An experimental gene therapy for retinitis pigmentosa made 7 of 10 blind patients more sensitive to light, according to a study published in October in the New England Journal of Medicine. The treatment pairs a single eye injection with camera goggles, and six of the patients improved enough for researchers to call the change clinically meaningful.

The work was led by José-Alain Sahel of the University of Pittsburgh and Botond Roska of the Institute of Molecular and Clinical Ophthalmology Basel (IOB), with funding from French biotech GenSight Biologics. It does not restore normal sight, but it is the first time the approach has worked in a group of patients rather than a single case.

How the Retinitis Pigmentosa Therapy Works

Retinitis pigmentosa is an inherited disease in which the retina’s light-sensing photoreceptors gradually stop working. Mutations in more than 100 different genes can cause it, which makes gene-by-gene fixes hard to scale.

Instead of repairing photoreceptors, the team used optogenetics. Each participant received one injection of an adeno-associated virus (AAV) vector into the worse-seeing eye. The vector carries the gene for ChrimsonR, a light-sensitive protein, into retinal ganglion cells. These cells normally pass visual signals to the brain and often survive even in advanced disease.

ChrimsonR responds to amber light, which is why patients wear special goggles. A camera captures the scene, a processor converts changes into pulses of amber light, and those pulses activate the treated cells.

What the Trial Found

• 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 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. 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.

Safety and Limits

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, which cleared within minutes after eye drops were given.

The approach also needs a working optic nerve, so it cannot help when the connection between retina and brain is damaged. The authors say larger trials are needed to confirm safety and efficacy.

What It Means for Patients

The result builds on a 2021 case in which one man treated with the same method could see and count objects. It also arrives as companies chase very different routes to artificial vision, including the brain implant behind Neuralink’s Blindsight.

Optogenetics avoids brain surgery and works regardless of which gene caused the disease. For now, it remains experimental and is not approved anywhere. Readers following genetic medicine can find more in our look at CRISPR and genetic engineering advances.

Earlier efforts to treat blindness, such as Neuralink’s first Blindsight plans, targeted the brain directly. This study shows the eye itself can still be part of the answer.

Source: IOB press release