FDA approves gene-editing treatment for sickle cell disease

NICK EICHER, HOST: Next up, greenlighting a gene-editing tool.

Back in December, the Food and Drug Administration approved a treatment for sickle-cell disease that relies on editing the DNA of patients.

MARY REICHARD, HOST: The technology behind this new treatment first made headlines just over a decade ago. In 2012, a team of American and French scientists discovered that sequences of genetic code in the immune system could be manipulated and edited using a special enzyme called CRISPR. That’s C-R-I-S-P-R.

Now the FDA says it’s safe to use a form of this gene-editing therapy called Casgevy for treating patients with certain blood disorders.

EICHER: How does it work, and is it good medical stewardship?

Joining us now is David Prentice (Phd). He’s Vice President of Scientific Affairs for the Charlotte Lozier Institute, and Advisory Board Chair of the Midwest Stem Cell Therapy Center.

REICHARD: David, thank you for joining us!

Well David, how does the CRISPR technology in the Casgevy treatment work to cure sickle cell disease?

DAVID PRENTICE: That's the actual therapy that's used, as you've mentioned. And what they do is they actually start with the patient's own adult stem cells. If we back up a step, you're, we're after trying to cure sickle cell disease and related types of diseases. Now, in the blood, the red blood cells are carrying oxygen. How do they do that? They've got little proteins called hemoglobin that grab onto the oxygen and then the cell carries around through your body. And the problem with sickle cell disease is there's a mutation, and it makes it number one not able to carry oxygen very well. But number two, the mutation makes those proteins clumped together into rod-like shapes, so it looks like a sickle. Casgevy was one for sickle cell. There's another one called Lyfgenia. Fancy-sounding names, but they get at sickle disease different ways. The Casgevy, the CRISPR based one really just goes in and it makes a cut to turn off an inhibitor of a different type of hemoglobin gene. Okay, there gets real complicated here, but if your listeners think about having a light switch, and you can turn it on and off turning on and off a gene would be the equivalent. In this case, there's a different type of hemoglobin called fetal hemoglobin. We use it while we're in the womb to get oxygen around to the cells of our body. And then it's turned off about the time we're born and the adult form is used. There's a cover over the switch that keeps fetal hemoglobin turned off once we're born. And what Casgevy does is go in and make a cut to turn off that cover so that you can now open up and make fetal hemoglobin. So the Casgevy is really just making fetal hemoglobin to carry the oxygen in place of the mutated normal adult globin. The other gene therapy that's just come out and been approved by FDA doesn't use the fancy CRISPR enzyme, but it takes the patient's own adult stem cells, and it inserts a new copy of the hemoglobin to replace the one that's mutated and causing all the trouble.

REICHARD: You know David, this conversation about gene-editing therapies reminds me of a story from 20-18. Back then, a Chinese scientist announced that he’d edited the genetic code of two unborn babies to prevent them from contracting H-I-V.

The scientist, He Jiankui [Haw jen-QUAY], was arrested by the Chinese government for illegal medical practices…but after being released in 20-22, he ended up back in the lab this past June. According to NPR, He [Ha] said his mistake was moving too quickly with his experiments.

David, what bioethical guidelines would you say are necessary as scientists do more with CRISPR?

PRENTICE: What your story about Dr. He points out is there actually two ways to do these genetic engineering therapies. One, the Casgevy and the Lyfgenia that we discussed are what are called somatic genetic engineering. You do this on somebody that's already born, or at least near birth, it only affects that individual, a nd you take care of their condition just as if you were giving them a particular drug, but again, you're changing their DNA. In this case, the other type, and what Dr. He did is called germline or heritable genetic engineering. And he actually started with those little girls when they were embryos, and did that genetic engineering on them at that point. Now, as you say, his idea was he was going to prevent them from being infected with HIV virus. It turns out only one of the two little girls did it actually work on them and the the treatment that they used, probably caused other types of changes, including making them more susceptible to influenza, West Nile virus, actually potentially changing their intelligence and probably changing the length of their lifespan, decreasing it. When you start messing around with something that will now be heritable and passed on to future generations, we don't really know what we're doing as scientists in the lab. And there is definitely an ethical distinction between doing these kinds of treatments on a patient who's already been born, and just treating them for a disease versus trying to change the future, if you will not just have one little individual, but generations.

REICHARD: A common argument for justifying scientific research in ethically murky areas like this is that the U-S can’t let adversary nations get ahead and potentially hurt us. That’s how we got nuclear weapons in the 20th century. How would you respond to that argument as it applies to gene-editing technology?

PRENTICE: Well, I think you know, the race is really to hold the highest standards of ethics. And in fact, if you look at lots of these various scientific studies that have been proposed, you have to look at what are you really after doing here? Are you really trying to alleviate a disease condition? Are you trying to design a human being in your own image? It turns out most of those techniques they propose and experiments that have been done, that crossed that ethical line are not the ones that work. Look at embryonic stem cells and the proposal that they were going to, as one person put it, cure all known maladies. Not a single person has been successfully treated and cured in 25 years of embryonic stem cell research, where in the meantime, adult stem cells from our own bodies or from matched donors, where you don't kill the donor as you do with embryonic stem cells, are the ones that are really treating disease and curing things. Currently, over 2 million people around the globe helped by adult stem cells. The scoreboard still reads zero for embryonic so the unethical research is also unsuccessful and we really need to focus on what's going to help people but without crossing the ethical lines.

REICHARD: David Prentice is the Vice President of Scientific Affairs for the Charlotte Lozier Institute. David, thank you for your time and expertise. We really appreciate it.

PRENTICE: Thank you.

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