For the first time, doctors have used a CRISPR gene editing therapy in an attempt to fix broken genes within the body, marking another step forward for a technology that promises to change how some inherited diseases are treated.
Clinicians at Oregon Health and Science University recently injected the therapy, developed by biotech Editas Medicine and partner Allergan, into the eye of a patient with a type of severe blindness, the companies confirmed Wednesday.
A study last year tested another CRISPR medicine in stem cells extracted from patients' blood, while a third trial previously used a different type of gene editing technology called zinc finger nucleases inside the body. But the patient recently given Editas and Allergan's therapy is the first to be treated using a CRISPR therapy that works in vivo.
The eye disease the companies hope to correct, called Leber cogenital amaurosis, is caused by mutations in any of at least a dozen genes. Editas and Allergan are focusing on just one particular type, known as LCA10. Between 2,000 and 5,000 patients in the U.S. and Europe have it, according to the companies.
"Half of the patients who have this disease are born essentially with light perception vision. They can tell that the room is dark or light," said Mark Pennesi, an associate professor of ophthalmology who is leading OHSU's involvement in the study, in an interview.
"The other half start at legal blindness and then will degrade over the first two decades of life."
Pennesi and his colleagues hope Editas and Allergan's medicine could restore vision by deleting the mutation that prevents the eye from making a protein critical to light-detecting cells.
If that protein is made again, the damaged segment of those photoreceptors should be able to regenerate, said Charles Albright, chief scientific officer at Editas, in an interview last month.
Editas and Allergan plan to enroll 18 adults and children into the study, which is currently being conducted at OHSU as well as centers in Miami, Boston and Ann Arbor, Michigan.
The initial focus will be on safety, as researchers gauge whether the CRISPR medicine being tested causes any side effects or toxicities. Should all go well with the first few adults given a low dose, Editas and Allergan will test four higher doses and potentially try the therapy in children.
Enrolling patients into the study, dubbed BRILLIANCE, has taken longer than the companies first expected when they opened the trial last July.
"Getting patients enrolled and recruiting has taken longer than planned," said Albright, noting there were prospective study participants who came in but ultimately weren't eligible for dosing.
Moving forward, Albright said enrollment should proceed more smoothly.
Whether the treatment helps improve vision will be measured using eye charts and a "mobility maze" similar to one used by Spark Therapeutics for its gene therapy Luxturna, approved in late 2017 for a different type of inherited blindness.
Luxturna works not by editing DNA, but rather by inserting a functional copy of a defective gene directly into the eye. That approach wasn't possible with LCA10, Pennesi said, because the gene in question is too large to fit into the inactivated viruses companies are using as delivery vehicles.
Editing DNA holds potential risks, however, the greatest being that the CRISPR therapy inadvertently cuts DNA in places the companies and researchers don't intend and makes irreversible changes.
As with all firsts, the long-term effects of gene editing aren't known either, although Albright noted that photoreceptor cells in the eye no longer divide, potentially making the results of Editas and Allergan's therapy more predictable.
While Editas and Allergan are first to the milestone of in vivo CRISPR editing, the field around them is quickly advancing.
CRISPR Therapeutics and Vertex, which are running the study that used a CRISPR therapy on extracted stem cells, already have initial data, while rival Intellia Therapeutics plans to begin this year a study of in vivo CRISPR editing in a rare disease known as transtheyretin amyloidosis.
Other, newer companies, meanwhile, are working to move past CRISPR and into more specific types of gene editing. One, the Cambridge, Massachusetts-based Beam Therapeutics, recently raised $207 million on the promise of its base-editing platform.
But the studies run by CRISPR Therapeutics and Editas, being the first in their respective settings, will be watched close.
"These are setting precedent," said Albright. "You're going to be seeing a lot more gene editing."