Blind patients want breakthrough gene editing experiments to restore their vision

Carlene Knight wants to do what most people take for granted, such as reading a book, driving a car, biking, watching animals at the zoo, watching a movie, and so on. She also longs to see the facial expressions of people.

“Especially to be able to see the face of my granddaughter, my granddaughter,” said 54-year-old Knight, who lives outside Portland. “It would be huge.”

Michael Kalberer wants to be able to read the computer screen so that he can get back to work as a social worker. He also hopes that one day he will see his niece and nephew play soccer instead of just listening and move around the world without help. But that’s not all.

“It may be audibly romantic and poetic, but you may be able to see the sunset again or see someone’s smile again,” said Calverer, 43, who lives in Long Island, New York. It’s a small thing I miss. “

Kalberer and Knight Breakthrough research Designed to try to restore vision to patients like them who are rarely suffering Genetic disease..

This study includes an innovative gene editing technique called CRISPRThis allows scientists to make precise changes to their DNA. Doctors believe that CRISPR can help patients fight many illnesses.It already shows the promise Blood disorders such as sickle cell disease Has been tested Some forms of cancer..

However, in these experiments, doctors remove cells from the body, edit them in the laboratory, and then inject the genetically edited cells into the patient.

The experiment volunteered by Knight and Kalberer is the first time scientists have used CRISPR to edit DNA while it is still inside the patient’s body.

“This is the first time anyone has actually tried to edit a gene from within the body,” he said. Dr. Lisa Michaels, Company Chief Medical Officer Sponsor researchEdit as Medicine, Cambridge, Massachusetts. “We are actually delivering a gene editing device to the part of the body where the disease is occurring and fixing it.”

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

“It’s kind of daunting to me,” Knight told NPR. “It’s not an everyday subject that people can say,’Oh, I changed my gene.’ “”

The first phase of the study that treated the first patient last year was designed primarily to assess safety. And so far, the procedure seems safe. By the end of the year, the researchers said they would share the first data on whether this procedure restored the patient’s vision.

“We are optimistic,” he said. Dr. Eric Pierce A member of Mass Eye and Year, a member of Mass General Brigham in Boston where Calverer was treated.

Why researchers turned to CRISPR

Knight and Calverer Leber Congenital Amaurosis, Destroys the light-sensing cells of the retina and destroys eyesight. A defect in a gene called CEP290 causes the disease version in which Knight and Calverer were born. According to Pierce, it affects about 1,500 people in the United States and about 15,000 to 30,000 people worldwide.

“I have no peripheral vision,” Knight said. “That is, you can’t see the sides at all. Only the size of the pencil lead looks straight.”

And her eyes are often out of control — this can be a symptom of LCA — even that small window is blurry.

The carbeller can only be seen through a small peephole. And his limited vision can suddenly blur, so it seems he’s looking through flooded swimming goggles, further obscuring his vision.

Both Kalberer and Knight are legally blind.

“I don’t have visual independence. I don’t have visual autonomy,” Kalberer said in the first interview of two interviews in September, just before the procedure. “The diagnosis may have broken me, and for a while it did.”

Because retinal cells are fragile and they try to edit them in the laboratory and return them to the body, doctors decided to use CRISPR to edit genes in the body. Traditional gene therapy is also impossible in this condition because the healthy version of the defective gene is too large to fit in the genetically modified virus used to carry the new gene to the human body.

Instead, doctors made three small incisions in Calverer’s right eye and Knight’s left eye, allowing billions of copies of the harmless virus to be injected. Each virus was designed to carry genetic instructions to produce a CRISPR gene editor within the retina.

“I was a little scared,” Knight said. “It was exciting and scary at the same time.”

It was hoped that CRISPR would act like a microscopic surgeon, literally cutting out genetic mutations in retinal cells. It should restore the function of light-sensing cells in the retina, prevent further vision loss, and possibly cause the production of proteins that may restore at least part of the blinded vision.

“Injecting billions of tiny viral particles under the retina to allow the patient to correct the spelling of genes in their own retina sounds like science fiction,” said Pierce of Mass Eye and Ear. Mr. says. “But that’s really happening.”

For patients, the potential of CRISPR is a “gift”

Researchers said the approach could provide a way to treat many other diseases that couldn’t even get cells out of the body, such as other eye diseases, brain diseases such as Huntington, and muscle diseases such as muscular dystrophy. ..

“Being at the forefront of science is very exciting,” he said. Dr. Mark Penesi, Associate Professor of Ophthalmology, Oregon Health & Science University, Portland, where Knight was treated.

As a safety precaution, doctors began by minimizing the number of viruses that carry out CRISPR commands in older patients who lose the least because their eyesight is already extensively damaged. The researchers also minimized the risk by treating only one eye in each patient.

“No one directly treated genetic editing inside the human body,” said Michaels of Editors Medicine. “And as a result, there [were] There are many concerns that taking these patients with limited vision may have put them at risk of disturbing or even losing their eyesight. “

Researchers have already treated four people and hope to add six more adults and eventually eight children. They are also testing gradually increasing doses.

Doctors compare the patient’s vision before and after surgery and between treated and untreated eyes to see if surgery helps improve the patient’s vision.

“It’s hard to express in words,” Calverer said. “You want it. You do your best, but to even have the potential-it’s a gift.”

Knight wants it to help her, or at least help researchers learn that the condition can benefit others, especially children.

“The possibilities are great,” she said. “It gives me hope.”

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