For the first time, scientists have used the gene-editing technique CRISPR to try to edit a gene while the DNA is still inside a person's body.
The groundbreaking procedure involved injecting the microscopic gene-editing tool into the eye of a patient blinded by a rare genetic disorder, in hopes of enabling the volunteer to see. They hope to know within weeks whether the approach is working and, if so, to know within two or three months how much vision will be restored.
"We're really excited about this," says Dr. Eric Pierce, a professor of ophthalmology at Harvard Medical School and director of the Inherited Retinal Disorders Service at Massachusetts Eye and Ear. Pierce is leading a study that the procedure launched.
"We're helping open, potentially, an era of gene-editing for therapeutic use that could have impact in many aspects of medicine," Pierce tells NPR.
The CRISPR gene-editing technique has been revolutionizing scientific research by making it much easier to rewrite the genetic code. It's also raising high hopes of curing many diseases.
Before this step, doctors had only used CRISPR to try to treat a small number of patients who have cancer, or the rare blood disorders sickle cell anemia or beta-thalassemia. While some of the initial results have been promising, it's still too soon to know whether the strategy is working.
In those other cases, doctors removed cells from patients' bodies, edited genes in the cells with CRISPR in the lab and then infused the modified cells back into the volunteers' bodies to either attack their cancer or produce a protein their bodies are missing.
In this new experiment, doctors at the Casey Eye Institute in Portland, Ore., injected (into the eye of a patient who is nearly blind from a condition called Leber congenital amaurosis) microscopic droplets carrying a harmless virus that had been engineered to deliver the instructions to manufacture the CRISPR gene-editing machinery.
Beginning in infancy, the rare genetic condition progressively destroys light-sensing cells in the retina that are necessary for vision. Vision impairment with LCA varies widely, but most patients are legally blind and are only able to differentiate between light and dark or perhaps to detect movement.
"The majority of people affected by this disease have the most severe end of the spectrum, in terms of how poor their vision is," Pierce says. "They're functionally blind."
The goal is that once the virus carrying the CRISPR instructions has been infused into the eye, the gene-editing tool will slice out the genetic defect that caused the blindness. That would, the researchers hope, restore production of a crucial protein and prevent the death of cells in the retina, as well as revive other cells — enabling patients to regain at least some vision.
"It's the first time the CRISPR gene-editing is used directly in a patient," Pierce says. "We're really optimistic that this has a good chance of being effective."
The study is being sponsored by Editas Medicine, of Cambridge, Mass., and Allergan, based in Dublin. It will eventually involve a total of 18 patients, including some as young as ages 3 to 17, who will receive three different doses.
"We're very excited about this. This is the first time we're doing editing inside the body," says Charles Albright, the chief scientific officer at Editas.
"We believe that the ability to edit inside the body is going to open entire new areas of medicine and lead to a whole new class of therapies for diseases that are not treatable any other way," Albright says.
Francis Collins, director of the National Institutes of Health, calls the advance "a significant moment."
"All of us dream that a time might be coming where we could apply this approach for thousands of diseases," Collins tells NPR. "This is the first time that's being tried in a human being. And it gives us hope that we could extend that to lots of other diseases — if it works and if it's safe."
Pierce, Albright and others stressed that only one patient has been treated so far and that the study, still at a very early stage, is designed primarily to determine whether injecting the gene-editing tool directly into the eye is safe.
To that end, the researchers are starting with lowest dose and the oldest patients, who have already suffered extensive damage to their vision. And doctors are only treating one eye in each patient. All of those steps are being taken in case the treatment somehow backfires, causing more damage instead of being helpful.
"CRISPR has never been used directly inside a patient before," Pierce says. "We want to make sure we're doing it right."
Still, he says, if the underlying defect can be repaired in this patient and others with advanced damage, "we have the potential to restore vision to people who never had normal vision before. It would indeed be amazing."
The study involves a form of Leber congenital amaurosis known as Type 10, which is caused by a defect in the CEP290 gene.
If the approach appears to be safe and effective, the researchers will start treating younger patients.
"We believe children have the potential to have the most benefit from their therapy, because we know their visual pathways are still intact," Albright explains.
The procedure, which takes about an hour to perform, involves making tiny incisions that enable access to the back of the eye. That allows a surgeon to inject three droplets of fluid containing billions of copies of the virus that has been engineered to carry the CRISPR gene-editing instructions under the retina.
The idea is that once there, the CRISPR editing elements would snip out the mutation that causes a defect in CEP290. The hope is that this would be a one-time treatment that would correct vision for a lifetime.
If it works, the volunteers in the study might be able to have the procedure repeated on the other eye later.
"If we can do this safely, that opens the possibility to treat many other diseases where it's not possible to remove the cells from the body and do the treatment outside," Pierce says.
The list of such conditions might include some brain disorders, such Huntington's disease and inherited forms of dementia, as well as muscle diseases, such as muscular dystrophy and myotonic dystrophy, according to Pierce and Albright.
"Inherited retinal diseases are a good choice in terms of gene-based therapies," says Artur Cideciyan, a professor of ophthalmology at the University of Pennsylvania, given that the retina is easily accessible.
But Cideciyan cautions that other approaches for these conditions are also showing promise, and it remains unclear which will turn out to be the best.
"The gene-editing approach is hypothesized to be a 'forever fix,' " he says. "However, that's not known. And the data will have to be evaluated to see the durability of that. We'll have to see what happens."
RACHEL MARTIN, HOST:
And now a major development in the world of science. For the first time, doctors have used a revolutionary gene-editing technique to try to treat a patient by editing their DNA while it is still inside their body. NPR health correspondent Rob Stein is one of the reporters following this story, and he joins us this morning. Hi, Rob.
ROB STEIN, BYLINE: Good morning, Rachel.
MARTIN: So scientists edited someone's DNA from inside their body, Rob?
MARTIN: Explain (laughter). How does that work? What does that mean?
STEIN: Yeah. So they've literally genetically modified someone from inside using a powerful new way to edit DNA called CRISPR. You know, and before this, scientists trying to use CRISPR to treat diseases had been taking cells out of patients' bodies, editing the DNA in the lab and then infusing the genetically modified cells back in.
STEIN: But now, for the first time, doctors didn't take any cells out of the patient. They figured out how to get this microscopic gene-editing tool inside the body to basically do a kind of genetic surgery on cells while the cells and the DNA is still inside the body - so to genetically modify someone from within.
MARTIN: That's amazing. How did this begin? I mean, how did we get to this point?
STEIN: They tried this first on someone with a rare, but terrible genetic disease that destroys key cells in the retina in the eye. So many people born with this are essentially blind. They can only maybe tell the difference between light and dark and maybe detect motion.
MARTIN: Wow. And so can you explain in layman's terms, as best you are able, the process of trying to fix this?
STEIN: Yeah, yeah. It's actually really fascinating. So a surgeon cut a tiny hole in the patient's eye, then dripped three little drops of liquid under the retina. Those drops had billions of a harmless virus that had been genetically engineered to carry the genetic coding for making the CRISPR gene-editing surgeon inside the retina, inside the cells.
STEIN: The CRISPR then, hopefully, literally cut out the genetic code causing the disease, letting the cells make a crucial protein that will hopefully heal the sick cells in the retina, giving the patient the ability to see. Here's Eric Pierce. He's a Harvard doctor running the study.
ERIC PIERCE: If we can fix the underlying genetic defect, we have the potential to restore vision to people who never had normal vision before. It would, indeed, be amazing.
MARTIN: I mean, the potential to restore vision - I imagine that there would be potential to address other ailments, other diseases, right?
STEIN: Yeah, that's right. That's right, you know? So that's why scientists are so excited about this. There are many other diseases that, you know, can't really be treated by taking cells out a patient's body and editing them and putting them back in - you know, brain diseases like Huntington's disease, maybe some inherited forms of dementia, muscle diseases like muscular dystrophy. So the hope is that this could be the beginning of a whole new era of medicine, which scientists take, you know - edit people's genes while the DNA's still inside their body to treat their diseases.
I talked to Francis Collins about this. He leads the National Institutes of Health.
FRANCIS COLLINS: All of us dream of what time might be coming where we could apply this approach for thousands of diseases. This is the first time that's being tried in a human being. And it gives us hope that we could extend that to lots of other diseases if this works and if it's safe. This is a significant moment.
MARTIN: Amazing. So what does happen right now?
STEIN: Yeah. So they did this procedure at the Casey Eye Institute - that's at the Oregon Health and Science University in Portland - and on the first volunteer in the study, you know, that was designed to test this. And the first thing that doctors and scientists are looking for is, you know, whether this is safe, you know?
Remember, nothing like this has ever been done before. So they're starting with a very low dose and an older patient who already can't really see very much. And they're only treating one eye. The idea here is just to make sure this doesn't backfire somehow and end up destroying whatever vision is left instead of helping. I talked to Charles Albright about this. He's from Editas Medicine, one of the companies sponsoring the study.
CHARLES ALBRIGHT: There's always a potential with any experimental medicine for things to happen that you don't anticipate. And so you always want to start in a situation where if something unexpected did happen, the chances of it causing damage is the least that you can possibly make it.
STEIN: So the scientists, you know, they're going to, hopefully, see if this patient starts to see better within weeks. But they'll be watching really closely. And if it does seem to be safe and it does seem to be working, they'll try higher doses on younger patients - even kids, who have the best chance this might actually help them the most.
MARTIN: All right. NPR health correspondent Rob Stein. Rob, thanks. We really appreciate it.
STEIN: You bet, Rachel.
(SOUNDBITE OF MARLEY CARROLL'S "STARLINGS") Transcript provided by NPR, Copyright NPR.