Simple tasks like riding a bike down the street or driving to the grocery store are a no-go for Carlene Knight. Afflicted with a rare genetic disease called Leber congenital amaurosis type 10 (LCA10), Knight, 55, has been legally blind since birth. She has no peripheral vision. “It’s an extreme tunnel vision,” she told The Daily Beast. “I kind of liken it to looking through a window with a tiny hole in it and trying to find something like a building outside.” Simple tasks like walking through a crowded room were arduous trials to avoid bumping into something and potentially injuring herself. At her office where she works at a call center, if she tried to walk around without her cane, she was constantly running into cubicles and tables and other objects all the time.
But the Happy Valley, Oregon resident has found her world opening up, ever since doctors literally fixed the DNA in the cells of her eyes.
By now you’ve probably heard of CRISPR, the gene-editing tool that’s taken the biomedicine industry by storm. CRISPR basically allows scientists to find a specific sequence of DNA inside a cell, and alter it. That opens up the possibility of treating and potentially curing a slew of illnesses and disorders caused by genetic mutations, like LCA10, which impairs the function of retinal cells. These kinds of cells can’t simply be removed, fixed, and plugged back into the eye. If they’re going to be fixed, it has to be in the body itself.
What happened to Knight is a huge step forward for physicians and researchers looking into CRISPR-related treatments. Up until now, the biggest breakthroughs in the space have revolved around taking unhealthy cells in patients, using CRISPR in the lab to modify them, and then putting them back into the patient. In this instance, CRISPR was used to directly edit the cellular DNA still inside of Knight and the others who participated in the trial.
“With any kind of new therapy being used on the human body for the first time, you always have to be cautious,” Mark Pennesi, an ophthalmologist at the Casey Eye Institute at the Oregon Health & Science University who led the experiment, told The Daily Beast. “There's the things you might know, and then there are the things you don't know. You have to always take a cautious approach.”
The trial was conducted jointly by the university and biotech company Editas Medicine, which specializes in gene editing. Preliminary trials on mice and non-human primates were safe and encouraging, so a clinical trial on humans with LCA10 was organized. The initial findings published Wednesday report the results for five participants (the other two having been treated only very recently). Two were given low doses of the new therapy, and three were given mid-range doses.
“When I was told about the trial, I was really excited because I wanted to help children whose lives could be enhanced with vision,” said Knight. “The hope is that if they have the procedure early enough, they’ll have a lot more vision later on life, while their neural pathways are developing.”
Knight, who received a mid-range dose, and another participant who received the low dose both found their vision significantly improving. Neither has normal vision, but Knight said she’s been amazed how much easier it is to do mundane things like find doorways, locate objects on the ground, and simply move around without having to surmount a myriad of hurdles. Colors are brighter and easier to see—to celebrate, she’s even dyed her hair green, her favorite color.
“It is amazing how the simple things can be so nice when you get them back,” she said.
Two out of five success stories is not the ideal outcome Pennesi was hoping for, and his team doesn’t have a clear explanation as to why not everyone who was treated saw improved vision. It could be the amount of dose, or factors specific to someone’s biology. And it might also be that patients need more time before the treatment works. “Even if the editing works, the brain kind of has to rewire itself to even recognize the improved cellular function,” he said. “That could take many more months for some people.”
The fact that none of the participants experienced any severe side effects is also a major milestone. Editas has started recruiting participants for higher dose trials, including children with LCA10. And the findings will likely be used as an encouraging sign for groups working on using CRISPR to treat other diseases where cells must be modified directly in the body, like Alzheimer’s, Huntington’s and Parkinson’s.
Knight’s vision continues to improve bit by bit since the procedure. “It’s going to be nice if I can see my granddaughter play and ride her bike and stuff like that,” she said. “I hope I could one day read a children’s book to her, with the large print. That would really be nice.”