Today, Explained - A cure for sickle cell?

Episode Date: May 6, 2022

Scientists have developed a long-sought treatment — perhaps even a cure — for sickle cell anemia. But getting it to patients might be an even bigger challenge. This episode was produced by Miles Bryan, edited by Matt Collette, fact-checked by Laura Bullard and Victoria Dominguez, engineered by Efim Shapiro, and hosted by Sean Rameswaram. Transcript at vox.com/todayexplained   Support Today, Explained by making a financial contribution to Vox! bit.ly/givepodcasts Learn more about your ad choices. Visit podcastchoices.com/adchoices

Noelle King, remind me what we did on Today Explained this week. This week. It's Friday. Certainly. Elon Musk. Monday was machine guns. We started the week by saying America has all of these machine guns on its hands now. Great show.

And then Tuesday was about another thing in news. Roe v. Wade. It was the thing. Roe v. Wade. Yes. Oh, my God. The biggest story in a generation. We had to throw out all our v. Wade. Yes. Oh, my God. The biggest story in a generation. We had to throw out all our plans.

Yes. To talk about. The leak. The leak. Which then you did again on Wednesday. Yes. And then Thursday. Kids.

Little kids. Always remember the little kids. Little kids who still don't have vaccines. That's right. Mm-hmm. It's a lot of grim news. It's a lot of grim news, dude. What do you say we end the week with a positive jam?

Oh my God, can we please? We have one, Noelle. What is it? We got a possible cure for sickle cell disease. No kidding! Coming up on Today Explained. Get groceries delivered across the GTA from Real Canadian Superstore with PC Express. Shop online for super prices and super savings.

Try it today and get up to $75 in PC Optimum Points. Visit superstore.ca to get started. Today, Today Explained. Today Explained, I'm Sean Ramos-Firm, and you'll be relieved to know that there's a doctor in the house. It's Dr. Dhruv Kular. I'm a physician at Weill Cornell in New York and a writer for The New Yorker. Where he recently wrote about a potential cure for sickle cell disease.

Yeah, so sickle cell disease is a disorder of the blood, and specifically the red blood cells, which carry oxygen to our entire body, to all organs in our body. And in most of us, these red blood cells are kind of like little saucers. You know, they can move around the body easily. They have no problem kind of dropping off their transport of oxygen. What happens with people in sickle cell disease is that a specific protein within the red blood cell, it's called hemoglobin. This is the protein that actually carries the oxygen. It's defective in some way. And so what it starts to do is instead of,

you know, if you can think about the red blood cell as kind of a bag with a bunch of little confetti inside and kind of move around okay, what happens with sickle hemoglobin is that it congeals into these long strands. And so it kind of stretches out the balloon of the red blood cell. It starts to look like what we call a sickle

or kind of a crescent moon. And that causes all sorts of problems. These types of red blood cells are fragile. They can't move their way through the body's blood vessels as easily. They cause kind of traffic jams. And the end result is that oxygen doesn't get to where it needs to be.

And so as you can imagine, that can cause all sorts of problems, strokes and joint damage and abdominal pain and bone pain. And the basic idea is that you're not getting enough oxygen to your different organs of your body. So sickle cell disease has been around forever. It was first kind of described in the early 1900s. And so in the article, I talk about a patient named Walter Clement Noel. And he's a gentleman from Granada. He comes to the United States to study dentistry at the University of Chicago.

And he has all sorts of medical problems. He has trouble breathing. He has pain in his abdomen. He has pain in his abdomen. He has pain in his joints. He ends up seeking care at a hospital in Chicago. It was by chance that Noel happened to consult James Herrick, a doctor with an interest in hematology, the study of blood. They look under the microscope and his blood has,

it doesn't look like, you know, normal red blood cells. It looks like all these little sickles. They follow him for three years. They can't figure out what it is, but they write a report. And in the coming decades, doctors around the country start to look at this report. They report similar types of symptoms in their own patients. And then in 1949, Linus Pauling describes what he calls the first molecular disease. I believe that this is the disease of the molecule and that if we look at the blood of these patients, we shall find that the hemoglobin molecules are different from those of other

people. So sickle cell disease was actually the first disease that we knew the exact protein, the exact molecule that was defective. So Dhruv, why did you want to write about sickle cell right now? So there's a few reasons. I mean, in my practice as a physician in the hospital, I often see patients who have sickle cell disease and they come into the hospital and they're in terrible pain often. It feels like somebody's hitting you with a hammer. They have all sorts of complications.

They can have strokes and joint destruction, and they're in the hospital, they're getting blood transfusions, and they need lots of pain medications. It is a really devastating disease. You know, anyone who kind of cares for patients in the hospital probably has experienced that. A lot of these patients are in and out of the hospital every few months. Some of them are in and out of the hospital every few weeks.

Nobody else but us, people that have pain, knows how it feels. And now, in the past few years, there's been these gene therapy trials, which seem incredibly promising. And so there have been dozens of patients treated through these types of gene therapies, which come in different kind of flavors that we can talk about. And many of these patients have had complete resolution of their symptoms. So they're not on pain medications. They don't have any further issues. And so I thought this was a really interesting set of potential therapies,

and I wanted to learn more about it. And it turns out they seem to be quite effective, but there's also a lot of challenges that may come up in terms of getting them to people. Unfortunately, for all sorts of reasons, sickle cell was underfunded for many years, and it didn't have any treatments for the next 50 years. And only now are we kind of getting to the point where we're really starting to get a handle on potentially transforming the care for people with sickle cell disease. What are some of the reasons it was so underfunded for so long? Who's most affected by sickle cell

disease? Yeah, so sickle cell disease affects predominantly people of African ancestry. And there's an important kind of reason for that. If you have one sickling gene, you have what's called sickle cell trait. And that affords a certain degree of protection against malaria. And so this gene kind of evolved in places in the world where malaria had a high prevalence. So in Africa, in Southern Europe, in parts of Asia, in the United States at least, the vast majority of people who have sickle cell disease are black. It's estimated that there's probably around 100,000 people in the U.S. with sickle cell disease. One in every 365 black births has sickle cell. And so it's really a problem that is related. You can't disentangle it from history of systemic racism and discrimination and bias within the medical system

and the funding for various treatments within the U.S. healthcare system. And for those reasons, it has been understudied and underfunded. So you're basically saying that the reason this hasn't really been addressed or a top priority is because it was mostly devastating black communities. It's one of the reasons. You know, cystic fibrosis, for instance, it affects about a third as many patients as sickle cell disease, but it receives much more in foundation funding than does sickle cell disease. You know, I talk about the ice bucket challenge you might remember back in 2014. Yo, maniacs, this is Hulk Hogan here, and this is the ice bucket challenge you might remember back in 2014.

Regrettably, I do remember that. It raised something like 100 times as much funding as sickle cell gets from foundations in a typical year. And so there was a real lack of funding for a very long time for this disease. So what you gonna do? Runs frozen. And so, previously, what tools have doctors had available to treat sickle cell disease? In 1998, there was the first medication that was approved. It was called hydroxyurea. It was approved by the FDA. As hematologists, we're frequently asked whether or not hydroxyurea is the best drug that we have available to treat our patients.

The truth is, it's really the only drug we have available to treat our patients, which is what makes it the best choice. And it's a medication that tries to shift some of the body's production from this abnormal sickle hemoglobin to a different type of hemoglobin, which is actually present just after we're born.

And that seems to help some people and it can reduce the number of times that people have sickling crises and the severity of those. It has some side effects. It doesn't work for everyone. That was the mainstay of treatment. There were some other adjunct therapies that people would use, like kids would get penicillin prophylaxis to guard against some infections. You'd want to make sure that they have their vaccines. But in terms of targeted treatment for sickle cell, that was the main one. And then a lot of patients, unfortunately, have to be on chronic pain medications, opioids often, to control kind of the severe pain that they have.

And so those were kind of a set of therapies that the doctors have been using and continue to use to care for patients with sickle cell. And now there's a game-changing treatment. There may be a game-changing treatment. We're on kind of the precipice, potentially, if these gene therapies are as effective as we think they are, of transforming care for patients with sickle cell disease. And there are a number of companies

that are in clinical trials with gene therapies. And those trials seem to be going quite well. Two of the companies that I in clinical trials with gene therapies. And those trials seem to be going quite well. Two of the companies that I've spoken with expect to submit their data for FDA approval at the end of this year or early next year. So it's possible that a year from now, we'll have several gene therapies for sickle cell disease on the market. And for people who don't know how gene therapies work, how do they work? It's hard to talk about them in general because for different diseases, there's different techniques.

But for sickle cell disease, I can tell you how it works. So for sickle cell disease, you can think of it almost like a stem cell transplant that you might have heard about for cancers or for other diseases. And so what happens is you take the patient's blood cells, you treat them in a lab, you edit the DNA of those blood cells. Meanwhile, the patients in the hospital, they've gotten chemotherapy to try to wipe out most of their bone marrow, both red blood cells and white blood cells. So during that period, they're at high risk for infection and other complications. And then you infuse their own blood cells back into them. These are now the

edited blood cells. The idea is that those blood cells will take up residence in the patient's bone marrow and start creating more of the hemoglobin afterwards. So this approach has kind of a few advantages as compared to traditional stem cell transplants. In a traditional transplant in the past that's been used for sickle cell as well, you need to find a donor, first of all. And not a lot of people have donors, so the estimates are, you know, less than one in five sickle cell patients can find a suitable sibling donor to go through this process. Even if you do find a donor, you end up having to take pretty powerful immunosuppressive medications because there's a risk that those new cells from someone else might be rejected by your body. And so you need to take these immunosuppressive medications, because there's a risk that those new cells from someone else might be rejected by your body. And so you need to take these immunosuppressive medications

that in and of itself can put you at risk for other types of infections. And so this is one of the reasons that these new gene therapies are so kind of exciting is that everyone is their own donor. There's very low risk of rejection going forward. And at least in the few dozen patients that we've seen, they've had quite good outcomes for the most part. Tell us about one of them. You know, one of the patients I spoke with was a woman named Victoria Gray. She was the first patient who got the CRISPR gene therapy in 2019.

And I'm 36 years old from Forest, Mississippi. Right now, I consider myself to be cured of sickle cell disease, but I will always consider myself to be a sickle cell patient. Well, I first started having sickle cell crisis at the age of three months old. So for me, it's been hospital stays my whole childhood in and out of the hospital with frequent blood transfusions and a lot of pain. And it's a pain that I couldn't rub and make feel better. I couldn't relieve it. Nothing helped except for high-dose pain medicines. And sometimes that didn't even help. And I would get pain in my chest that felt like lightning strikes.

It would take my breath away. I had a crisis during testing, and I had to be hospitalized in Nashville. So Dr. Frangu came to my bedside, and he said, Victoria, have you ever heard of something called CRISPR? And I said, no. And he said, it's a new therapy. And if you agree to do it, you will be the first. If I hadn't went through 34 years of sickle cell disease, I wouldn't even know or relate to being a sickle cell patient now. You know, I don't have any of the symptoms at all. I'm able to do all the things I dreamt of doing. I don't have pain crisis at all.

I was released from the hospital in September of 2019, and I haven't had a hospital admission since then. My favorite thing has been being there for my kids. And that's being in the audience, in the crowd at the football games, watching my daughter cheer and my boys on the field, even smiling when they're on the bench. So that's been the greatest part. And as I can say, when I speak to other sickle cell patients who are considering this,

I can dream again. I stopped dreaming as far as my future, because all I saw was pain, devastation, and failed dreams, so I stopped. Now I can dream, I can plan, and look forward to life and growing old. As you might remember from recently, even when science delivers a cure, not everyone always wants it. How to deal with that in a minute on Today Explained. Support for Today Explained comes from Aura. Aura believes that sharing pictures is a great way to keep up with family,

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you gonna do when Hulk Hogan runs frozen? We're back. Today explained Hulk Hogan, What you gonna do? Runs frozen. We're back. Today explained Hulk Hogan, Sean Ramos from Dr. Dhruv Kular, who practices medicine but also finds time to write for The New Yorker. Extremely annoying, but he's a good guy. Who's been telling us about what seems like a potential miracle treatment for sickle cell disease.

Unfortunately, this is America, so I had to ask Dr. Dhruv what this treatment costs. They're not on the market yet, but the expectation is that each treatment is going to cost one to two million dollars per patient. So these are going to be incredibly expensive treatments. You know, I should note that the lifetime costs of someone with sickle cell disease, because it's such a treatment-intensive condition, already are in that neighborhood, $1 to $2 million. So it's not clear how this will shake out in terms of just dollars and cents. But obviously, if you're able to avert all the human costs and the human toll of going through

a lifetime of treatment and a lifetime of hospitalization, that's clearly a net benefit. And I'm guessing that makes sickle cell disease treatment cost prohibitive for a lot of Americans. You know, that's a complicated question because, you know, a lot of these costs will be borne by insurers and not necessarily by the individuals who are getting the treatment. About half of patients in the United States who have sickle cell disease are on Medicaid.

Medicaid eligibility and benefits vary a lot state to state. And so a lot of the states that have the highest African-American populations also have the most restrictive Medicaid program. So there's a lot of concern in the sickle cell community and among physicians and patients that these therapies will be restricted. You know, Medicaid agency might say you have to be this old, you have to have this much disease, but you can't have that much

disease to get these therapies. And so the high price of these therapies, I think will be a real issue from a policy perspective. And we need to figure out how we're going to make sure that it's accessible to patients. Are there challenges aside from cost to making this kind of groundbreaking treatment available to as many people as possible? Absolutely. I mean, cost is a huge problem, but I think there's a number of other things that we're going to have to grapple with in the coming years. I mean, one is just this infrastructure problem. And so, you know, right now, a lot of patients in the U.S. who have sickle cell disease, they don't have a regular source of care. They don't have a hematologist.

They're not even getting the treatments that are kind of the basic standard of care that people with sickle cell disease should get. So getting them this wildly expensive, very resource-intensive new therapy, that's a whole other level of challenge that I think our health system has to grapple with. And we need to really invest in making sure that people are connected to healthcare, that they're connected to the specialists that they need, that they're able to get to the centers that are doing this type of therapy.

Not every hospital will obviously be doing this. So there's a real infrastructure challenge. There's also a real trust challenge. I mean, many people with sickle cell have been treated very poorly. Black Americans have faced discrimination. They've faced medical experimentation that's been unethical. They've been denied treatment. As a result, Black Americans have lower levels of trust in health care than do white Americans. And having sickle cell disease, when I would go to receive treatment, a lot of times I was labeled as a drug seeker. So they would delay my treatment.

And there have been times where I waited in pain in the emergency room for over six hours before I received treatment and I spoke to nurses and some of them were good nurses and they would tell me not to repeat what they said but it's like the main reason you're not getting treated is not because of your disease but because of your skin color and I even had a friend she was the first person I ever met that had sickle disease other than myself you know she was a few years older than me. By the time I made it to 18, I think she had turned 21 and she had her own place. It was my first year in college and I planned to stay the summer with her. But before summer came, she passed away.

She had a sickle cell crisis. She didn't want to go to the emergency room because of the treatment. And she tried to treat herself at home by taking Tylenol and specifically Tylenol PM. She ended up going into a coma and never woke up. that was because the hassle when you go there and you're in pain and the people you're looking to for help are the ones who judge you I've been speaking to sickle cell patients and they call me brave for even trusting the process to doing it because it's like you didn't feel like they were just going to experiment on you. There has to be open communication there and trust. They have to trust us if they want us to trust them. On top of the challenges with trust, with cost, with infrastructure,

there's our recent experience with the COVID-19 vaccines, which a lot of people famously didn't want to get. It makes me feel sort of skeptical about gene therapy for sickle cell disease. That's one of the real kind of insights that I was trying to bring out in this article. An incredible therapy that exists is not the same as one that actually helps people. And so, you know, as you mentioned, we've had these extraordinarily effective COVID vaccines that came to market within a year of the pandemic starting. And they're free. You can get them while you're waiting for your train. It takes a minute to get. And yet, millions of people have chosen not to get them. With sickle cell gene therapies, the situation is much, much more complex. This is a therapy that requires a prolonged hospital stay.

It's one that costs millions of dollars. It's one that you're literally editing people's genes. And so the ideas of mistrust and trust are going to be incredibly important. And we need to take kind of steps now. We need to think ahead about, it's not just going to be sickle cell disease, but hopefully in the coming decade, there will be gene therapies for other diseases as well. And how do we start to socialize some of these kind of innovative therapies? How do we get people to start to feel comfortable with them? How do we talk honestly about the risks, but also the tremendous benefits? Dr. Dhruv Kular, he recently wrote about sickle cell disease in The New Yorker. His article is titled, Are We About to Cure Sickle Cell Disease?

Miles Bryan produced our show today. Laura Bullard fact-checked it. Efim Shapiro mixed and mastered. Paul Malnzy chipped in on the engineering, too. Matthew Collette edited. The rest of our team here at Today Explained includes Amina Alsadi. She's our supervising producer. Noelle King, you know who she is.

We got producers Halima Shah, Heidi Mawagdi, Victoria Chamberlain. We got VP of Audio Liz Kelly Nelson. Lots of help this week from Lauren Katz, Ode White. Music from Breakmaster Cylinder and Noam Hassenfeld on the radio across these United States in partnership with WNYC. I'm Sean Ramos for M Today Explained is part of the Vox Media Podcast Network. Thank you.