This Gene-Editing Experiment Allows Patients with Vision Loss to See Color Again
Click to enlarge the image and toggle caption Franny White/OHSU Franny White/OHSU
Carlene Knight had such poor vision that she could not even use her cane to maneuver around the call center she works in.
Knight, who was born with a rare genetic condition that affects the eye, says "I was bumping into cubicles and really frightening people that were sitting there."
This has changed since she volunteered to take part in a groundbreaking medical experiment. Her vision has improved to the point that she can see colors, identify doors, navigate through hallways, spot objects, and make out what is behind them.
It's great. Knight laughs, "I don't scare people" and "I don't have as many bruising on my body."
Knight is one of seven patients suffering from a rare eye condition who agreed to allow doctors to modify their DNA using the cutting-edge gene-editing tool CRISPR. Doctors inject the CRISPR directly into their cells. Knight and another volunteer from the study gave exclusive interviews to NPR about their experiences.
CRISPR is being used for the first time in this manner by researchers. In the past, cells were removed from the bodies of patients and edited in the laboratory before being infused back into them.
Researchers revealed Wednesday the first evidence of the treatment's effectiveness in improving vision for patients suffering from the severe form, Leber congenital aurosis or LCA.
Professor of ophthalmology at Oregon Health & Science University, Dr. Mark Pennesi says that "it's a really incredible technology and very powerful." The results were presented at the International Symposium on Retinal Degeneration, Nashville, Tenn.
Pennesi warned that patients must be treated more frequently and monitored for longer periods of time to ensure safety and determine how effective the treatment is. The researchers are excited about the results and have given permission to proceed to the next patient group.
Knight's vision has improved dramatically since she received the experimental treatment. She no longer has to look blindly for objects. Instead, she can just look.
She recalled that she dropped a fork recently on her kitchen floor. It's really cool."
Also, colors are brighter and more vivid.
"I have always loved colors. It's something I have enjoyed since I was a child, even though I only had a limited amount of vision. She says that I now see how brighter they were when I was a child. It's amazing.
Knight, 55, lives outside Portland, Oregon. She dyed her hair green to celebrate.
She laughs and says "It's fun to see,"
LCA is caused when a genetic mutation disables key cells of the retina. LCA is a progressive loss in vision that occurs at birth and usually results in legal blindness. Although the treatment cannot cure all patients, the results of the trial are substantial enough to make a significant impact on daily life.
Click to enlarge the image and toggle caption Mass Eye & Ear Mass Eye & Ear
Michael Kalberer was another volunteer who participated in the experiment. He can now see colors for first time in many years. It was only about a month later that he noticed the difference when a red car passed him. The most dramatic moment was on the dance floor at his cousin's wedding.
Kalberer says, "I could see my cousins dancing with me changing colors and I was able to identify the DJ's strobe light changes." It was a joyful, fun moment.
Kalberer, a 43-year-old Long Island resident, is able to recognize shapes and light better. He also regained his peripheral vision which makes it easier to do simple tasks like ordering food at a restaurant.
It has made it easier to navigate a plate of food or stab food. Kalberer says that if I look at a plate of food and see a spoon or utensil inside, I can see the edge of that utensil from the outside of the plate or bowl. These changes are very important to me.
He even can finally see sunsets again. After the treatment, he recalls seeing one for the first time. After a meal with friends, he was returning home when he noticed pink in the sky.
She said, "Yeah, I see the sunset. That's sunset. Kalberer said that they both smiled at one another. It was a wonderful moment.
Kalberer noticed colored lights on the dancefloor of his cousin's wedding. He said, "That was that was that was very, very joyous moment."
CRISPR has already been shown to be effective in treating blood disorders such as sickle disease, beta thalassemia, and other severe diseases. Doctors are also trying to use CRISPR to treat cancer. These experiments involve taking cells from the body and editing them in the laboratory before infusing them into patients. Because cells from the retina cannot be removed and then inserted back into the eye, it is impossible to do this with LCA.
Doctors genetically modified a virus that was harmless to carry the CRISPR gene-editor. They then infused billions more modified viruses into the retinas in Knight's left and Kalberer’s right eyes, along with five other eyes. In case of an emergency, the procedure was only performed on one eye. After the research is completed, the doctors will treat the other eye.
Once CRISPR had been found in the cells of the retinas' cells, it was hoped that it would remove the genetic mutation that caused the disease and restore vision by activating dormant cells.
Dr. Eric Pierce is the director of Massachusetts Eye & Ear's ocular genomics center and Harvard Medical School professor of ophthalmology who's leading the test of the method.
"We are thrilled to see early signs that gene-editing works. Pierce states that this is the first time evidence has been found that gene-editing is working inside someone, and in this instance it is improving their vision function.
Patients were followed for three to nine months and the procedure failed for them all. It could have failed because the patient received too little or because of their vision problems.
Click to enlarge the image and toggle caption Mass Eye & Ear Mass Eye & Ear
Kalberer received the lowest dose and one volunteer was given a higher dose. Improvements began to show around four to six weeks following the procedure. Knight and another patient who had received a higher dose showed improvement in navigating a maze. It's too early to know what the outcome will be for two other patients.
None of the patients has seen a significant improvement in their vision. Researchers say that the patients are seeing a significant improvement. There have been no side effects.
To ensure safety and to know how this treatment might help, many more patients will need to be followed.
Researchers have started to administer a higher dose of the drug, which may work better. They also plan to eventually start treating children who are most likely to benefit.
They are also optimistic that the vision of patients who have been treated so far will improve over time.
Pennesi states that sometimes the brain can't recognize and use the improved vision because of changes in the function of the retina. It takes time to master the art of using that better vision.
These findings could be used to treat other diseases that doctors cannot take cells from, such as Huntington's disease and muscular dystrophy.
It's thrilling. The world is our oyster. We almost have too many targets to pursue," Dr. Lisa Michaels (chief medical officer at Editas Medicine), who is sponsoring this study, says.
Knight and Kalberer, for their part are thrilled to see at least a little more.
Kalberer states, "I feel incredibly honored and privileged that I am part of this, as well as very, very excited, hopefully, to see what the future holds."
