First U.S. Patients Treated With CRISPR As Human Gene-Editing Trials Get Underway

Apr 16, 2019
Originally published on May 31, 2019 6:46 am

The powerful gene-editing technique called CRISPR has been in the news a lot. And not all the news has been good: A Chinese scientist stunned the world last year when he announced he had used CRISPR to create genetically modified babies.

But scientists have long hoped CRISPR — a technology that allows scientists to make very precise modifications to DNA — could eventually help cure many diseases. And now scientists are taking tangible first steps to make that dream a reality.

For example, NPR has learned that a U.S. CRISPR study that had been approved for cancer at the University of Pennsylvania in Philadelphia has finally started. A university spokesman on Monday confirmed for the first time that two patients had been treated using CRISPR.

One patient had multiple myeloma, and one had sarcoma. Both had relapsed after undergoing standard treatment.

The revelation comes as several other human trials of CRISPR are starting or are set to start in the U.S., Canada and Europe to test CRISPR's efficacy in treating various diseases.

"2019 is the year when the training wheels come off and the world gets to see what CRISPR can really do for the world in the most positive sense," says Fyodor Urnov, a gene-editing scientist at the Altius Institute for Biomedical Sciences in Seattle and the University of California, Berkeley.

Here are highlights of the year ahead in CRISPR research, and answers to common questions about the technology.

What is CRISPR exactly?

CRISPR is a new kind of genetic engineering that gives scientists the power to edit DNA much more easily than ever. Researchers think CRISPR could revolutionize how they prevent and treat many diseases. CRISPR could, for example, enable scientists to repair genetic defects or use genetically modified human cells as therapies.

Traditional gene therapy uses viruses to insert new genes into cells to try to treat diseases. CRISPR treatments largely avoid the use of viruses, which have caused some safety problems in the past. Instead they directly make changes in the DNA, using targeted molecular tools. The technique has been compared to the cut and paste function in a word processing program — it allows scientists to remove or modify specific genes causing a problem.

Is this the same technique that caused a recent scandal when a scientist in China edited the genes of two human embryos?

There's an important difference between the medical studies under discussion here and what the Chinese scientist, He Jiankui, did. He used CRISPR to edit genes in human embryos. That means the changes he made would be passed down for generations to come. And he did it before most scientists think it was safe to try. In fact, there have been calls for a moratorium on gene-editing of heritable traits.

For medical treatments, modifications are only being made in the DNA of individual patients. So this gene-editing doesn't raise dystopian fears about re-engineering the human race. And there's been a lot of careful preparation for these studies to avoid unintended consequences.

So what's happening now with new or planned trials?

We've finally reached the moment when CRISPR is moving out of the lab and into the clinic around the world.

Until now, only a relatively small number of studies have tried to use CRISPR to treat disease. And almost all of those studies have been in China, and have been aimed at treating various forms of cancer.

There's now a clinical trial underway at the University of Pennsylvania using CRISPR for cancer treatment. It involves removing immune system cells from patients, genetically modifying them in the lab and infusing the modified cells back into the body.

The hope is the modified cells will target and destroy cancer cells. No other information has been released about how well it might be working. The study was approved to eventually treat 18 patients.

"Findings from this research study will be shared at an appropriate time via medical meeting presentation or peer-reviewed publication," a university spokesperson wrote in an email to NPR.

But beyond the cancer study, researchers in Europe, the United States and Canada are launching at least half a dozen carefully designed studies aimed at using CRISPR to treat a variety of diseases.

What other diseases are they testing treatments for?
Two trials sponsored by CRISPR Therapeutics of Cambridge, Mass., and Vertex Pharmaceuticals of Boston are designed to treat genetic blood disorders. One is for sickle cell disease, and another is a similar genetic condition called beta thalassemia.

In fact, the first beta thalassemia patient was recently treated in Germany. More patients may soon get their blood cells edited using CRISPR at that hospital and a second clinic in Germany, followed by patients at medical centers in Toronto, London and possibly elsewhere.

The first sickle disease patients could soon start getting the DNA in their blood cells edited in this country in Nashville, Tenn., San Antonio and New York.

And yet another study, sponsored by Editas Medicine of Cambridge, Mass., will try to treat an inherited form of blindness known as Leber congenital amaurosis.

That study is noteworthy because it would be the first time scientists try using CRISPR to edit genes while they are inside the human body. The other studies involve removing cells from patients, editing the DNA in those cells in the lab and then infusing the modified cells back into patients' bodies.

Finally, several more U.S. cancer studies may also start this year in Texas, New York and elsewhere to try to treat tumors by genetically modifying immune system cells.

What can go wrong with CRISPR? Are there any concerns?

Whenever scientists try something new and powerful, it always raises fears that something could go wrong. The early days of gene therapy were scarred by major setbacks, such as the case of Jesse Gelsinger, who died after an adverse reaction to a treatment.

The big concern about CRISPR is that the editing could go awry, causing unintended changes in DNA that could cause health problems.

There's also some concern about this new wave of studies because they are the first to get approved without going through an extra layer of scrutiny by the National Institutes of Health. That occurred because the NIH and FDA changed their policy, saying only some studies would require that extra layer of review.

"Every human on the planet should hope that this technology works. But it might work. It might not. It's unknown," says Laurie Zoloth, a bioethicist at the University of Chicago. "This is an experiment. So you do need exquisite layers of care. And you need to really think in advance with a careful ethical review how you do this sort of work."

The researchers conducting the studies say they have conducted careful preliminary research, and their studies have gone through extensive scientific and ethical review.

When might we know whether any of these experimental CRISPR treatments are working?

All of these studies are very preliminary and are primarily aimed at first testing whether this is safe. That said, they are also looking for clues to whether they might be helping patients. So there could be at least a hint about that later this year. But it will be many years before any CRISPR treatment could become widely available.

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For the first time, scientists have used the powerful new gene-editing technique called CRISPR to try to treat sick people in the U.S. NPR health correspondent Rob Stein broke this news. He's here in the studio to tell us the details.

Welcome, Rob.

ROB STEIN, BYLINE: Oh, hey there.

CORNISH: What can you tell us first about the patients who were treated?

STEIN: Yeah, so there were two patients who were treated so far. Both have cancer. One has the type of blood cancer known as multiple myeloma. And the other has a type of tissue cancer known as sarcoma. And both had suffered relapses after undergoing other standard cancer - kinds of cancer treatments before undergoing this experimental treatment with CRISPR.

CORNISH: So you said it's experimental. How did doctors use CRISPR to do the treatment here?

STEIN: Yeah, so what they did is they removed key immune system cells - they're known as T cells - from each patient. And then they used CRISPR to edit the DNA inside these T cells in the lab. And then they infused the genetically modified cells back into the patients' bodies. And the idea is that these edits in the DNA would kind of turn these T cells into - you can sort of think of them as guided missiles that would zero in and attack then destroy any cancer cells in their bodies.

CORNISH: What do we know about how well it worked?

STEIN: Yeah, so unfortunately, they're not releasing, really, any information so far about how well it worked. What we do know is that these patients were treated as part of the first study that was approved in this country to try to use CRISPR to treat people with a medical problem. It's being conducted at the University of Pennsylvania. And the university is only saying that these researchers are going to wait to release any details at some point in the future at a medical meeting or by publishing them in a scientific journal.

CORNISH: Forgive me for saying this, but that sounds cagey (laughter). Can you talk about why they might be holding back?

STEIN: Yeah. So, you know, these scientists - they're being very careful. They know how new and experimental this is. And therefore, it's got - has some risks. Whenever you try something this new and this powerful this early, you never know what's really going to happen when you try it in patients. And this study is actually being done at the University of Pennsylvania.

And it's the same university where, in the early days of gene therapy, a young man did die in a very early gene therapy study that set the field back, like, a decade. So the last thing these researchers want to do is, you know, do anything risky. They're taking it very carefully, being very slow. They're going to follow these patients for a long time to see if it's safe and how well it's working.

CORNISH: All right. There's a lot at stake here. And this isn't the only study, I understand, that's trying to use CRISPR to treat diseases. What else is going on?

STEIN: Yeah, yeah. It's actually a really exciting time for - in the world for CRISPR and medical treatments right now. There's about a half a dozen studies that are - have been going in China for cancer for a while. And now another half a dozen or so are being launched in Europe, in the United States and in countries like Canada that try to treat a variety of diseases. In the first one are blood disorders. One is known as beta thalassemia. That first patient was treated there in Germany recently. And then there's - another trial is going to be starting soon in this country to try to use CRISPR to treat sickle cell disease. So it's a lot happening right now with CRISPR and diseases.

CORNISH: And it sounds like it's still early days.

STEIN: It is early days. And that's really important to point out; that these are very preliminary studies. They're aimed primarily at trying to find out if this is safe. But they are going to follow these patients to see how well it's working for clues. We might get a sense of that by the end of this year or maybe early next year.

CORNISH: That's NPR's health correspondent Rob Stein.

Thanks for your reporting.

STEIN: Oh, sure - nice to be here. Transcript provided by NPR, Copyright NPR.