Blind Patients Recover Partial Vision in Gene Therapy Trial

The patients sit perfectly still as a needle inches toward one of their eyes. After the injection, they’ll no longer be completely human. The syringe is filled with a gene therapy that installs a light-sensitive algae protein into failing retinas and could reboot some lost vision.

When scientists first proposed using algae proteins to restore human eyesight, the idea seemed like science fiction. Could alien proteins integrate into our intricate visual system? Even if they did, could the brain translate the resulting signals into sight, rather than nonsensical bursts of light?

A new study suggests yes, with caveats. The team treated people with retinitis pigmentosa, a genetic disease that gradually destroys light-sensing cells in the retina. Seven of ten patients showed improved light sensitivity. After patients donned goggles that deliver pulses of light to activate the algae proteins, the team tested their eyesight. Roughly half could reach for and touch objects or identify the orientation of a black bar, a common test of visual recovery.

The treatment is still far from restoring full vision. What patients saw was too blurry and the field of view too narrow to discern texture or fine detail. The boundaries of objects looked squiggly. But those who responded to the treatment continued to improve over roughly five years. One participant, whose story made headlines in 2021, can now recognize and count different objects, and white stripes on a crosswalk pop out.

The study, called PIONEER, is an ambitious clinical trial combining gene therapy with optogenetics. The first goal was to assess safety, and it met the mark. Most participants experienced a brief bout of inflammation in the eye receiving the injection. The only patient to suffer a severe side effect was quickly treated with medication.

The findings suggest the initial success wasn’t a fluke. The study “represents an important milestone for optogenetic vision restoration,” said study author Stefan Futterknecht at the Institute of Molecular and Clinical Ophthalmology Basel, in a press release.

Setting Sights High

Around two decades ago, Karl Deisseroth was hunting for new ways to control brain cells. Electrical bursts and chemicals, which are how neurons communicate, seemed like obvious choices. But nature had something stranger to offer: algae.

Algae produce a protein called channelrhodopsin. When activated by light, the protein changes neuron activity using a mechanism that works similarly in mammalian cells. In a foundational paper, Deisseroth’s team inserted the protein into rodent neurons, and voilá—the neurons could now be controlled using light.

The technology, called optogenetics, revolutionized neuroscience.

By genetically tagging specific neurons with channelrhodopsin, scientists can now dial the cells’ activity up or down like a dimmer switch. Optogenetic experiments have revealed brain circuits that shape feelings, memory, and cognition with unprecedented precision.

Researchers panning for more genes in different algae strains struck gold again. One channelrhodopsin variant they found, ChrimsonR, was particularly exciting. Unlike the classic version that’s activated by blue light, ChrimsonR responds to amber light, which penetrates tissues better and is less damaging. More recently, scientists have begun to use generative AI to redesign natural proteins to make them even more sensitive to light.

“Optogenetics provides opportunities for mapping the brain in a way that we could once only dream of,” said Per Svenningsson, Chair of the Nobel Committee for Physiology or Medicine, when the technology won the coveted prize this year.

Still, it has mainly been considered a research tool.

Light It Up

Retinitis pigmentosa gradually robs people of their eyesight. Researchers have linked over 100 genetic variations to the condition, which kills off light-sensitive cells in the retina.

“The replacement (or editing) of a single gene would not help most persons,” wrote Deisseroth in the New England Journal of Medicine. Instead, adding channelrhodopsin could offer a more universal solution by rewiring surviving neurons.

Early successes bolstered the idea. In one study, scientists equipped cones—a type of retinal light-sensing cell—with channelrhodopsin in mice with retinitis pigmentosa. The therapy boosted their light sensitivity. It also reactivated cones that had stopped responding to light in human retina samples.

The new study took a different approach. In advanced disease, cones may have already degenerated beyond the point at which they could be saved. So instead, the gene therapy targeted ganglion cells. These cells process signals from light-sensitive cells and pass that information to the brain, but don’t detect light themselves. Ganglion cells are, however, more resilient than cones. Add channelrhodopsin, and they could become substitute light sensors.

The team packed genetic instructions for ChrimsonR into a harmless viral delivery system and injected it into the poorer seeing eye of 10 patients aged 40 to 73. All were legally blind, and each received one of three escalating doses.

As the patients gradually built up levels of the algae protein in their eyes, the team faced another challenge: Translating visual scenes from the outside world into amber light that the engineered ganglion cells could recognize.

They developed specialized goggles that look a bit like Apple’s Vision Pro. The goggles use a camera to scan the field of view thousands of times per second, monitoring for light changes in every pixel. When the device detects a change, it pulses amber light from that pixel into the eye. Because our eyes naturally dart around—often without us noticing—this dynamic method may better mimic normal vision.

With the goggles on, 6 of 10 participants showed clinically meaningful improvement in light sensitivity, with more than a fourfold boost over baseline readings. One participant improved over 62-fold. Of the eight who agreed to further eyesight tests, roughly half could touch a notebook, grab a small staple box, and detect changes in a rotating bar.

Of those who initially responded to the treatment, improvements lasted for years. Their brains also seemed to adapt to the alien light sensors. In one test, participants were asked to open or close their eyes while looking at a tumbler. Electrical brain signals related to vision were more coherent with eyes open, suggesting their perception depended on improved visual input.

Any gene therapy carries risk. In an already worsening eye, inflammation and other side effects could cause further damage. Overall, the injection appeared relatively safe. Most participants experienced a temporary increase in eye pressure, but no detectable side effects throughout the body. The retina’s overall structure remained unchanged. One person suffered a blockage in a major eye artery that cleared within minutes after treatment with an FDA-approved eye drop.

For now, the participants still can’t read or see faces. The therapy reaches only a fraction of their ganglion cells, making sharper vision harder to restore. More advanced versions of channelrhodopsin with greater light sensitivity may increase resolution.

As for the hardware, the team is working on versions of the goggles that deliver more accurate and timely stimulation. Potential upgrades include an eye tracker, software to preprocess visual scenes, and even holographs.

“Overall, although optogenetic methods have been developed primarily for basic science discovery,” wrote Deisseroth, they’re now heading towards “diverse therapeutic approaches.”

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