Gene-editing experiment allows these patients with vision loss to see colors again

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Carlene Knight’s vision was so poor that she couldn’t even maneuver around the call center where she works using her cane.

“I was bumping into the booths and really scaring people sitting in front,” says Knight, who was born with a rare genetic eye condition.

But that changed after volunteering for a landmark medical experiment. Her vision has improved enough that she can make out doors, navigate hallways, spot objects, and even see colors.

“It’s good. I don’t scare people and I don’t have as many bruises on my body,” Knight laughs.

Knight is one of seven patients with a rare eye disease who have volunteered to let doctors edit their DNA by injecting the revolutionary gene-editing tool CRISPR directly into the cells still present in their bodies. Knight and another study volunteer gave exclusive interviews to NPR about their experience.

This is the first time that researchers have worked with CRISPR in this way. Previous experiments had removed cells from patients’ bodies, modified them in the lab, and then injected the modified cells back into patients.

On Wednesday, researchers revealed the first evidence that the approach appears to be working – improving the vision of at least some patients with the condition, known as Leber congenital amaurosis, or ACL, a severe form of visual impairment.

“It’s really amazing and very powerful technology,” says Dr. Mark Pennesi, professor of ophthalmology at the Casey Eye Institute at Oregon Health & Science University. He presented the findings at an international retinal degeneration symposium in Nashville, Tenn.

More patients will need to be treated and monitored

Pennesi warned that more patients need to be treated and followed up longer to confirm the approach is safe and to determine how well it can help patients. But the current results are so promising that the researchers got the green light to move on to the next group of patients.

Knight’s vision is much clearer and brighter since receiving the experimental treatment. Instead of having to reach out blindly to find items, she can simply search for them.

Recently, for example, when she dropped a fork on her kitchen floor, she said, “I just bent down to pick it up and didn’t know where it was and just saw it by. earth. It’s very cool.”

The colors are also much brighter and more vivid.

“I’ve always loved colors. Ever since I was a kid, it’s one of those things I could appreciate with just a tiny amount of vision. But now I realize how much brighter they were when I was a kid. because I can see them much brighter now,” she said. “It’s just amazing.”

So Knight, who is 55 and lives outside of Portland, Oregon, dyed her hair her favorite color, green, to celebrate.

“It’s quite fun to watch,” she laughs.

ACL is caused by a genetic mutation that disables crucial cells in the retina. Patients experience progressive vision loss from birth that usually renders them legally blind. The treatment is far from curing the patients in the trial, but the changes some have experienced are significant enough to have a significant impact on their daily lives.

Michael Kalberer, a volunteer in the experiment, can now see colors and has regained more peripheral vision. (Eye and Ear Mass)

Another experiment volunteer, Michael Kalberer, can also see colors for the first time in years. He noticed it about a month after the procedure when a red car drove by. But the most dramatic moment happened on the dance floor at her cousin’s wedding.

“I could see the DJ strobe lights changing colors and identify them with my cousins ​​dancing with me,” Kalberer says. “It was a very, very fun happy moment.”

Kalberer, who is 43 and lives on Long Island, can also recognize shapes and light much better and he has regained more peripheral vision, which makes simple things like eating out much easier.

“It made it easier for me to navigate a plate of food and stab it a little easier. If I look at a plate of food and there’s a spoon or utensil in it, I can see the edge of it. utensil outside the bowl or plate,” Kalberer says. “So these changes are very, very important to me.”

That first sunset was a highlight

He can even finally watch the sunsets again. He remembers the first time he saw one after the treatment. He was returning from a meal with a friend when he saw pink in the sky.

“She’s like, ‘Yeah, you see the sunset. It’s sunset. And we both smiled at each other,” Kalberer said. “It was a great moment.”

CRISPR already shows promise for treating devastating blood disorders such as sickle cell disease and beta-thalassemia. And doctors are trying to use it to treat cancer. But these experiments involve removing cells from the body, editing them in the lab, and then injecting them back into patients. This is impossible for conditions like ACL, because the cells of the retina cannot be removed and then reintroduced into the eye.

So the doctors genetically modified a harmless virus to carry the CRISPR gene editor and infused billions of modified viruses into the retinas of Knight’s left eye and Kalberer’s right eye, as well as one eye of five other patients. The procedure was performed on one eye just in case something went wrong. Doctors hope to treat the patients’ other eye once the research is complete.

Once CRISPR was inside retinal cells, the hope was that it would suppress the genetic mutation causing the disease, restoring vision by reactivating dormant cells.

“We’re thrilled about this,” says Dr. Eric Pierce, director of the Massachusetts Eye & Ear Ocular Genomics Institute and professor of ophthalmology at Harvard Medical School, who is helping lead the experiment testing the approach.

“We are excited to see the first signs of efficacy because it means gene editing is working. This is the first time we have evidence that gene editing is working inside someone and that it improves – in this case – his visual function,” Pierce says.

it didn’t work for everyone

The procedure did not work for all patients, who were followed for between three and nine months. The reasons it didn’t work could be that their dose was too low or maybe their vision was too damaged.

Michael Kalberer takes an exam at Massachusetts Eye and Ear. (Eye and Ear Mass)

But Kalberer, who received the lower dose, and a volunteer who received a higher dose, began to report improvement starting about four to six weeks after the procedure. Knight and another patient who received a higher dose improved enough to show improvement on a battery of tests that included navigating a maze. For two others, it is too early to tell.

None of the patients regained normal vision, far from it. But the improvements are already making a difference for patients, say the researchers. And no significant side effects occurred.

Many more patients will need to be treated and followed up for much longer to make sure the treatment is safe and how much it might help.

Researchers have started giving a higher dose, which may work better, and are possibly considering starting to treat children, who have the best chance of benefiting.

They are also optimistic that the vision of patients treated so far may improve over time.

“When you improve retinal function, sometimes there’s a delay in the brain’s ability to recognize and use that vision,” says Pennesi. “It takes time to learn how to use this enhanced vision.”

The results could open the door to using the same approach to treat other diseases where doctors cannot remove cells from the body, including brain disorders such as Huntington’s disease and muscle diseases such as muscular dystrophy.

“It’s exciting. The world is our oyster. We have almost too many targets we can hit,” says Dr. Lisa Michaels, chief medical officer at Editas Medicine, which is sponsoring the study.

For their part, Knight and Kalberer are simply delighted to be able to see at least a little better.

“I’m incredibly honored and privileged to be a part of this, and very, very excited to literally hopefully see what happens in the future,” Kalberer said.

Copyright NPR 2022.

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