Researchers from the OHSU Casey Eye Institute in Portland, Oregon, have broken new ground in science, medicine, and surgery — the first gene editing procedure in a living person. For the first time, scientists are altering DNA in a living human. With more research the study could lead to the development of procedures that can help to correct other genetic disorders. Known as the BRILLIANCE clinical trial, the procedure is designed to repair mutations in a particular gene that causes Leber congenital amaurosis type 10, also known as retinal dystrophy. It is a genetic condition that results in vision deterioration and has previously been untreatable. “The Casey Eye Institute performed the first gene editing surgical procedure in a human being in an attempt to prevent blindness from a known genetic mutation,” said Dr. Mark Fromer, ophthalmologist at Lenox Hill Hospital in New York. “The abnormal DNA is removed from a cell with the generating mutation. This will potentially offer sight to people with a form of previously untreatable blindness.” How does retinal dystrophy gene correction work? Retinal dystrophies are degenerative genetic diseases of the retina. These conditions manifest themselves over time with side effects like color blindness or tunnel vision and can eventually lead to complete blindness. “If one of the genes needed for vision is misspelled, the cells get sick and die. The goal of this procedure is to fix the correct spelling of one of the misspelled genes that causes generation, which would, in turn, allow the cells to restore their health and restore vision,” said Dr. Eric Pierce, leader of the BRILLIANCE trial and Massachusetts Eye and Ear Director, Inherited Retinal Disorders Service, and Harvard Medical School William F. Chatlos Professor of Ophthalmology. CRISPR is a technology that can be used to edit genes. The CRISPR acronym stands for Clustered Regularly Interspaced Short Palindromic Repeat, which refers to the organization of certain DNA sequences. The technology was designed to locate a specific piece of DNA inside a cell and alter it. During the BRILLIANCE clinical trials, researchers were able to snip out the abnormal DNA in cells that are responsible for causing this particular type of retinal degeneration. The procedure does not change the genetic code of a person, but changes the DNA in a localized area of the retina. How is this procedure different from other genetic treatments? Other genetic treatments, such as those for sickle cell disease, have previously been carried out “ex vivo,” or outside the body. Cells are extracted and treated before being inserted back into patients. As part of the BRILLIANCE trials, these treatments are happening directly in a patient’s eyes. “Since it is the first time that this is being done, the key question has been, ‘Can this be done safely in people?’,” said Dr. Pierce. “The answer can be yes. Even if that doesn’t sound like a lot, it’s a really important step.” Why is this a groundbreaking achievement? Developing potential therapies, whether genetic or not, involves testing at many levels. The testing starts in labs, but until it is tested in people, physicians can never be sure if they will work or will be safe. “Testing any drug or any therapy in people is a big step,” said Dr. Pierce. “It makes it especially important because the biomedical research community thinks that this has potential for treating many genetic disorders. We can’t realize any of that potential unless we can do the treatment in people safely.” The treatment has been approved for clinical trials to begin testing in humans. If it is effective at restoring vision for subjects in the trial, the next step would be Phase 3 trials to see if it is possible to have it approved as something that can be performed on the public to treat this condition. Patients with this particular type of retinal dystrophy may be able to see a day when treatment will be possible to prevent, halt, or reverse blindness for them, and for their children, as well. Altering the DNA means that it stops it in its tracks and prevents it from replicating in future generations. What is even more exciting is the roadmap this could lay for future gene therapies. Dr. Mark Pennesi, chief of the OHSU Casey Eye Institute’s Paul H. Casey Ophthalmic Genetics Division, said in a statement that the importance of this first use of CRISPR in vivo is that it could have potential to be used beyond ophthalmology. Potential for the future “This groundbreaking stay opens the door to the possibility of treating genetic mutations for different medical disorders through gene editing,” added Dr. Fromer. “The door has opened for genetic therapies of many other genetic conditions, not only retinal diseases, but others that affect muscle systems like muscular dystrophy, which we haven’t been able to treat with gene therapies so far,” said Dr. Pierce. A human reminder When ground-breaking science makes headlines, it’s easy to overlook the human input that went into making it happen. The excitement over the potential often outweighs the human risk that goes into making it safe for the general public. “I’ve become much more aware of this as I do these clinical trials,” said Dr. Pierce. “The people who volunteer to participate are really pioneers. They’re helping us and all of humanity. You can’t make progress without them. We need to recognize how brave they are and how valuable their contributions are. You can do all the science in the world, but you can’t do much without people who are willing to let us try the treatments.” Source
