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A major breakthrough in treating a genetic disorder can be credited to our next guest. Sickle cell disease is a blood disorder that affects more than 20 million people worldwide. Theyve recently had a breakthrough. Federal News Networks Eric White spoke to one of the scientists at the National Institutes of Health conducting research on sickle cell on Federal Drive with Tom Temin. Dr. John Tisdale is a finalist in this years Service to America Medals program.

Dr. John Tisdale: I trained in internal medicine, and that was in the early 90s. I encountered patients with sickle cell disease who were experiencing extraordinary pain. And at that time, all we had was pain medication. So we would give pain medication and IV fluids because very often dehydration was what provoked the pain episode in these patients. But we had no specific treatments, nothing that were directed at the disease itself, only management of the pain. It was strange to me because I had learned about sickle cell disease in genetics classes and had known that we knew the basis for this disease longer than any other disease, yet we had no treatment, nothing. So it motivated me to think about ways that could treat the disease. The obvious thing that came to mind was a bone marrow transplant because we had a very active bone marrow transplant service at Vanderbilt. And I found that a very exciting way to approach disease and it just made sense that if you have a blood disease that causes all this difficulty in blood comes from the bone marrow well one obvious way to fix it is just to replace the bone marrow with one that doesnt have the genetics that causes the disease, like a brother or sister that we were doing for other kinds of diseases, and that could potentially cure the disease. And in fact, I learned that it had been done before in a patient who had leukemia. And that was a reason for her getting a bone marrow transplant. But she also had sickle cell disease and she was cured of both. There were some efforts during that time to bring that to the clinic, in the pediatric setting, and everything is always easier with kids because theyre tougher when it comes to medications and transplants and all the things that you can think of doing, chemotherapy. That got me motivated into studying hematology and bone marrow transplant, and trying to figure out ways to bring bone marrow transplant to patients with sickle cell disease.

Eric White: This sickle cell disease, obviously weve all heard of it. Even if you know what it is, its still a complicated disease. Can you explain what is the latest research says that sickle cell disease actually does over? As I said its a very strange disease that affects the body in many different ways. Are there any new findings as to how it does actually affect it?

Dr. John Tisdale: Well, I think weve known for a very long time exactly what happens in this disease. It arose as a way to protect from death from malaria. So just one little letter off for the gene that makes our hemoglobin, and hemoglobin is the molecule in red blood cells that carries oxygen around the blood. So one letter off in part of that molecule, and you have protection from malaria, you dont get the very severe form of malaria because the red cell is not as hospitable to the parasite. So that gets selected for in areas where theres malaria, like in Sub Saharan Africa. But if you get two copies of the gene, one from mom and one from dad, you get this disease, sickle cell disease because the hemoglobin now is different than the normal hemoglobin. Instead of carrying oxygen around and staying in solution like it does normally, you have a hemoglobin that once it does its job by dropping off oxygen out in the body, it can come out of solution and become like rock hard, distort the shape of the red cell thats normally squeezing through blood vessels to find its way back to the lungs to get more oxygen. When that happens, block the circulation. So it kind of causes a log jam and all the blood behind it gets stuck. And so wherever that happens, gets starved of its oxygen. So I mean, if it happens in the brain, for example, it causes a stroke. And so kids, eight years old can have a stroke that looks exactly like the sort that we see in the elderly who have vascular disease. If it happens in the muscle, its extremely painful or in the bone. And it happens in every organ in the body. And as a result can damage those organs over time and significantly shorten the lifespan of patients with sickle cell disease. So the lifespan currently is in the 40s. And thats much improved over the last several decades, but its still much lower than then people without the disease.

Eric White: So with your research, what has given you the most promise? What results have you all hung on to whether its bone marrow transplant or gene therapy? Is there one that you say hey, we might be on to something here?

Dr. John Tisdale: Well, I think the biggest breakthrough that weve made is figuring out just how much of the bone marrow we have to fix. So it turns out, we dont have to completely replace the bone marrow with somebody elses bone marrow to make the blood normal. So normally in a bone marrow transplant you you have to give chemotherapy to take away all of the cells that are making blood. Thats kind of like tilling the garden, right? You cant go out in the middle of a cornfield and spread a bunch of tomato seeds and expect to have tomatoes there, theyre not going to grow because the corns already growing. So the thinking is to do a bone marrow transplant, you have to harvest the corn, till the soil, plant the sees. And the same is true for bone marrow transplants. But it turns out for sickle cell disease, we dont have to do that. Weve had patients who even though we try to get rid of all their bone marrow, we failed and they had up to 80% of their own bone marrow still making blood, and presumably sickle blood. But if we had only 20% from the donor that was making normal blood, that would result in all of the blood being normal. And thats just because sickle cells live 10 or 12 days in the circulation, normal cells live 120 days in the circulation. And since the normal cells have such an advantage, you dont really have to completely eradicate the patients own bone marrow or you dont have to fix every cell. So thats important. That told us two things. One, we dont have to use toxic chemotherapy that we normally have to use to do a bone marrow transplant. And furthermore, we can start to think about gene therapy as an approach because we know we can never fix every cell. But if we could fix 20% of cells, we would predict from what weve observed in patients getting transplants from their brother or sister, that wed be able to fix the disease. And were well above the 20% mark when we transfer genes into cells. We can also correct the mutation at higher than 20%. So knowing that we only have to get to 20% has allowed us to start clinical trials, using the patients own bone marrow where we take those seeds out and try to fix them and give them back. If we can make 20%, we think we can fix the disease.

Eric White: Is there anything else that youd like to get the word out on? Is there any way people might be able to help or if if they have any family members who are suffering from this, if theres anything you would like to tell them?

Dr. John Tisdale: Well, I mean, I think the thing thats very important to understand for anyone with a genetic disease or otherwise is that clinical trials are the way that we make progress. And so participating in clinical trials is important for moving the field forward, and we partner with our patients and their family and their support structure to do these clinical trials and to make progress in the disease. So its extraordinarily important for people to understand that. Thats the way we make progress.

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NIH scientists credited with breakthrough in treating a genetic disorder - Federal News Network