Progress, Not Cure, for Sickle Cell Disease, Says Ethicist

This transcript has been edited for clarity.

Hi. I'm Art Caplan. I'm the chair of the Division of Medical Ethics at New York University Grossman School of Medicine in New York City.

There has been exciting and somewhat hyped news, as you'll see in a minute, about sickle cell disease. Some of you may remember back to medical school days that sickle cell disease is when an individual has both bad mutations that cause sickling of blood cells produced by bone marrow.

Sickle cell trait is when you have only one of the mutations. In fact, most biologists think sickle cell appeared as a way to combat malaria. People with the trait are far more common. They seem to have resistance against the parasite owing to their partial or occasional sickling of their blood cells. This disease blocks their circulation, causes extreme pain, and is really an awful thing to live with.

Well, many people have argued that there hasn't been much of a market or an interest in trying to chase down sickle cell disease cures. Some even worry that maybe it's because it's a disease that almost exclusively impacts people of African American descent, both here and in Africa.

The good news is that there have been many efforts underway in the biotech realm to find some way to genetically engineer the problem of sickle cell disease so that it doesn't impact those affected. Some breakthroughs have taken place.

New techniques such as CRISPR, where we have single gene edits going on, have shown that if you take bone marrow out of an individual with sickle cell disease, the bad form of sickle cell, put it in a lab, put in the little genetic scissors, and take out the gene that controls, if you will, blood formation by the stem cells in bone marrow and get that out of the way, those cells revert to making fetal hemoglobin — which is great because it doesn't sickle.

Then you knock out the rest of the bone marrow in the individual; bring it back; put in the new, altered stem cells that are now making fetal hemoglobin, and you've got a person who, in theory, is cured. You don't have any more bone marrow in them that makes the bad sickling cells. You've only got these new altered cells in the bone marrow that make fetal hemoglobin.

Another company has a technique wherein they still use a viral vector to try to modify cells that are making blood cells, the stem cells — but there, they're putting in a message to say, don't make sickling cells. They're inserting a message that says, make normal blood cells. There are two strategies.

This has all gotten a tremendous amount of attention. Sickle cell is a massive public health problem both here and overseas. Many announcements were made that we have a cure and we've got the treatment. I think we have to be careful when talking to patients about what's going on.

Both techniques are still experimental. They've been put through clinical trials, and the FDA fast-tracked them and said they were very impressed with the benefits that both of the interventions obtained for people. However, we haven't had long-term follow-up. Both techniques could lead to situations where the genetic modifications are not confined to the cells you're trying to change &mdash let's say the bone marrow stem cells making blood cells &mdash but they hit something else and they cause adverse events.

We have to watch for that over time to see whether there are some later effects of genetic engineering that just weren't anticipated. Certainly, techniques that use viral vectors to try to modify cells have had some of that problem. We are not ready yet to say that this is an absolute, safe cure.

There's another major problem. The Casgevy intervention with CRISPR has a $2.2 million estimate to pay for it. The Lyfgenia viral vector has a $3.4 million estimate to pay for it. These are obviously huge hurdles for almost everyone in the US, and I would say even a bigger percentage will be unable to get access in Africa or elsewhere, where sickle cell disease is a huge problem.

Not only is the cost challenging, but also are the techniques of getting the bone marrow out, changing it in the lab, destroying the remaining bone marrow with chemotherapy, then putting everything back. It's months of very rigorous, tough, demanding interventions. Many places just don't have the capacity to use this kind of stage forum of genetic engineering.

I'm not against, by any means, celebrating the first steps toward curing sickle cell disease and toward eliminating it as a blight on humankind. I also think we're in baby steps. You shouldn't run around suggesting to people we have the cure or the answer.

Part of the answer isn't just that it worked in a clinical trial. Part of the answer is that it's affordable. Part of the answer is that we can refine the technique so we don't have to go through four or five separate stages involving all kinds of specialists and clinics to basically perform what is the world's most complicated bone marrow transplant.

We're not there yet in terms of a cure for all, but we did make progress and that's a wonderful thing. We don't want people or patients who have sickle cell thinking they saw it on the news, it's done, but where is it for them. We can't say that right now. That kind of cure just isn't here yet.

I'm Art Caplan at the Division of Medical Ethics at New York University Grossman School of Medicine. Thank you very much for watching.

Medscape Business of Medicine © 2024  WebMD, LLC

Any views expressed above are the author's own and do not necessarily reflect the views of WebMD or Medscape.

Cite this: Arthur L. Caplan. Progress, Not Cure, for Sickle Cell Disease, Says Ethicist - Medscape - Feb 22, 2024.