Blind Patients Hope Landmark Gene-Editing Experiment Will Restore Their Vision

Carlene Knight would love to do things that most people take for granted, such as read books, drive a car, ride a bike, gaze at animals in a zoo and watch movies. She also longs to see expressions on people's faces.

"To be able to see my granddaughter especially — my granddaughter's face," said Knight, 54, who lives outside Portland, Ore. "It would be huge."

Michael Kalberer yearns to be able to read a computer screen so he could get back to work as a social worker. He also hopes to one day watch his nieces and nephews play soccer instead of just listening to them, and move around in the world without help. But that's not all.

"Maybe be able to — as romantically poetic as this sounds — see a sunset again, see a smile on somebody's face again. It's the little things that I miss," said Kalberer, 43, who lives on Long Island in New York.

Kalberer and Knight are two of the first patients treated in a landmark study designed to try to restore vision to patients such as them, who suffer from a rare genetic disease.

The study involves the revolutionary gene-editing technique called CRISPR, which allows scientists to make precise changes in DNA. Doctors think CRISPR could help patients fighting many diseases. It's already showing promise for blood disorders such as sickle cell disease and is being tested for several forms of cancer.

But in those experiments, doctors take cells out of the body, edit them in the lab and then infuse the genetically edited cells back into patients.

The experiment Knight and Kalberer volunteered for marks the first time scientists are using CRISPR to edit DNA when it's still inside patients' bodies.

"This is the very first time that anyone's ever actually tried to do gene-editing from inside the body," said Dr. Lisa Michaels, chief medical officer at the company sponsoring the study, Editas Medicine of Cambridge, Mass. "We're actually delivering the gene-editing apparatus to the part of the body where the disease takes place in order to correct it."

NPR is the first news organization to interview any of the patients participating in the unprecedented experiment.

"It's mind-boggling to me," Knight told NPR. "It's not an everyday subject where people can say, 'Oh, I had my genes altered.' "

The first stage of the study, which treated the first patient last year, was designed primarily to assess safety. And so far, the procedure appears to be safe. By the end of the year, the researchers said they expect to share the first data on whether the procedure restored any vision for the patients.

"We're optimistic," said Dr. Eric Pierce of Mass Eye and Ear, a member of Mass General Brigham in Boston, where Kalberer was treated.

Why researchers turned to CRISPR

Knight and Kalberer were born with a form of Leber congenital amaurosis, which destroys light-sensing cells in the retina, devastating vision. A defect in a gene called CEP290 causes the version of the disease with which Knight and Kalberer were born. It affects as many as about 1,500 people in the U.S. and about 15,000 to 30,000 people worldwide, according to Pierce.

"I have no peripheral vision whatsoever," Knight said. "That means I cannot see off the side at all. I can only see straight ahead about the size of a pencil lead."

And her eyes often jump around uncontrollably — which can be a symptom of LCA — making even that tiny window blurry.

Kalberer can only see through a tiny peephole, too. And his limited view can suddenly blur, so it's as if he's looking through a swimming goggle that's been flooded, further obscuring his vision.

Both Kalberer and Knight are legally blind.

"I do not have visual independence. I do not have visual autonomy," Kalberer said during the first of two interviews, which occurred in September just before undergoing the procedure. "The diagnosis could have broken me. And for a while it did."

Doctors decided to try using CRISPR to edit a gene inside their bodies because retinal cells are too fragile to remove, edit in a lab and try to return to the body. Traditional gene therapy is also impossible for this condition because a healthy version of the defective gene is too big to fit into the genetically modified viruses used to ferry new genes into people's bodies.

Instead, doctors made three small incisions in Kalberer's right eye and in Knight's left eye so they could infuse billions of copies of a harmless virus. Each virus had been engineered to carry genetic instructions to manufacture the CRISPR gene-editor inside their retinas.

"It was a bit scary," Knight said. "It was exciting and scary at the same time."

The hope was the CRISPR would act like a microscopic surgeon, literally slicing out the genetic mutation in cells in their retinas. That should trigger production of a protein that could restore the function of the light-sensing cells in their retinas, preventing any further loss of vision and possibly restoring at least some of their lost vision.

"It sounds a bit like science fiction to be injecting billions of tiny little virus particles under the retina so that they can go make spelling corrections of the gene inside a patient's own retinal cells," said Pierce of Mass Eye and Ear. "But it's really happening."

For patients, CRISPR's possibility is a "gift"

Researchers said the approach could offer a way to treat many other diseases where it's also not possible to take cells out of the body, including other eye disorders, brain diseases such as Huntington's, and muscle diseases such as muscular dystrophy.

"It's just so exciting to be on the cutting edge of science," said Dr. Mark Pennesi, an associate professor of ophthalmology at the Oregon Health & Science University in Portland, where Knight was treated.

As a safety precaution, doctors started by using the lowest number of viruses carrying the CRISPR instructions in older patients, who had the least to lose because their vision was already extensively damaged. The researchers also minimized risk by treating only one eye in each patient.

"No one had ever done direct treatment of gene-editing inside the human body," said Michaels of Editas Medicine. "And as a consequence, there [were] a lot of concerns whether by taking these patients who have limited vision we might have had risks such as disturbing the vision and even loss of the little bit they had."

The researchers have already treated four people and are hoping to add six more adults and eventually eight children. They are also testing gradually increased doses.

Doctors are comparing the patients' vision before and after the procedure, and between their treated and untreated eyes to see if the procedure is helping them see better.

"It's hard to put into words," Kalberer said. "You hope for it. You do the best you can. But to even have the possibility — it's a gift."

Knight hopes it will help her, or at least help researchers learn things that could benefit others with the condition, especially children.

"The possibilities are wonderful," she said. "It makes me hopeful."

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