Stem Cell News
In Depth Interview: Cord Blood for Diabetes
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Interviewed: Desmond Schatz, MD. University of Florida
Posted: November 6, 2008
What is type 1 diabetes?
Dr. Schatz: Type 1 diabetes is an autoimmune disease, meaning that your own body's white cells attack and kill your body's pancreas. In essence, it is a suicide of the pancreas. The destruction of the pancreas is unique just to those cells that make insulin. This suicide attacks the pancreatic beta cells. Those are the cells that make insulin. The patient who develops type 1 diabetes -- usually children and also, now we are finding more and more in adults, cannot make any insulin. If you do not have any insulin -- blood sugars -- your glucose tends to rise in your blood and that starts causing problems such as drinking a lot, urinating a lot, eating a lot and losing weight at the same time. It is a disease that is characterized by high blood glucose and has, unfortunately, short term and long term complications.
How serious is type 1 diabetes?
Dr. Schatz: It is a serious disease affecting both the individual as well as society. Right now, the cost of diabetes -- type 1 and type 2 -- is one in seven healthcare dollars. The cost of diabetes in the United States is in excess of about $174 billion, but if was only cost it would be okay. If one looks at it, children and adults have to take insulin shots four, five, six times a day they have to wear a pump. They have to check their blood glucose four, five, six times a day. They have to watch what they eat and they have to come and see the doctor every three or four months, and no matter what they do, it seems like it is not good enough. If that wasn't enough, there is an increased risk of complications. The lifespan of a person with diabetes is shortened 15 to 20 years due to accelerated atherosis due to hardening of the blood vessels, heart attacks, strokes. Patients with diabetes are likely to develop complications such as blindness, nerve damage and numbness. There are over 80,000 amputations just from diabetes per year, 15 to 20,000 cases of blindness and kidney failure every year just from diabetes, so clearly we need to do something to both prevent and cure this disease.
Where did the idea to do the cord blood study come from?
Dr. Schatz: It is a great story, actually. I got a phone call from a parent about four years ago and he called me up and said Dr. Schatz, I want to talk to you about a study he had recently seen in Nature and I asked which paper he was talking about. I read the paper and I saw that what they had done was that they had given bone marrow to animals that had been rendered diabetic and there was an improvement in the diabetes. He basically called me up and asked if I would give this drug to his child or would I give that drug, and I said no. He asked if I would I consider this and I said probably not. He said, "Well I want you to think about doing this. I have stored cord blood in my child. I believe it is safe. Is there anything to lose?"
We discussed it as a group and we looked at the rationale. We clearly thought that it was safe and we decided to write them a one person protocol and this person was infused with cord blood from that particular child and that child seemed to do better. As a result, we said if it is worked in this particular child, let's devise a study to recruit patients from over the country and the world to participate in this research study. Together with my colleague Dr. Haller, we initiated a protocol. We got approval from the FDA and we got funding from the Juvenile Diabetes Research Foundation and subsequently from the National Institutes of Health to initiate a study on 20 children to ask the question, if we are to infuse their cord blood back into them, could we in fact improve the metabolic control? We have no expectation that it is going to reverse it. We are asking the question can we in fact, improve it by whatever method? We do not really understand the mechanism that we can to improve the outcome. So we started that study. We have now recruited 18 or 19 patients from throughout the United States, Canada and Mexico. We are now following children for an average of about a year and it appears just from the studies that there is an improvement in metabolic control and patients are doing well. People are very happy that they have participated in the study and the compliance has been outstanding.
Results have also shown they require less insulin, correct?
Dr. Schatz: I think that they are very preliminary and I want to emphasize the nature, because sometimes we get a little hyped into what we are finding. We are comparing the group to a retrospect. In other words, we designed this study to randomize it, meaning that some people would go on cord blood and other people would get nothing. All we have are those patients who got cord blood and we have compared them to a group who are similarly aged matched and matched for duration of disease. If we compared those two groups, the preliminary data would suggest that they have better control and they have less insulin dosages -- at least six and one year after receiving the cord blood; but I will also emphasize that it is very difficult because the control group. These are very inspired parents. For someone who has stored their cord blood and then come as far as San Francisco, Kansas, Canada or Mexico, to here, they are obviously a very, very compliant family. They are very inspired families and they are going to do whatever they can. It may be that the cord blood is not working and it is just that these are just a selected group of people. That is something obviously we are very aware of. Because we cannot do a controlled study here in the United States, what we have done is set up collaborations with colleagues in Finland and Germany, where they are going to be looking at a control group in a pro-active fashion.
How many times was the cord blood infused?
Dr. Schatz: One time because that is all you have. That's the limitation. We thought it would be very difficult to get families, but it actually has not been difficult to get 20 people. We have enrolled these 20 people in a couple of years so that has been really good. We have actually had a lot more people, but they were reluctant to want to do it until we definitely showed that there was number one, an effect, and number two, that it is a one time thing. Once you use it, the cord blood is gone. It cannot be used for any purpose in the future because it is gone.
How does the cord blood process work?
Dr. Schatz: When a child is born, the parents have made the conscious decision to store their cord blood. Together with their OB and a reputable cord blood company, as much blood as they can get from the umbilical cord is taken and stored. It costs the family both an initial fee to obtain it and then to store it for however long of a period. Those families have self-selected. We do not have a program that we can store cord blood, although I think this should be something that we should consider if, in fact, the study proves successful.
They take the cord blood and it is stored in the early parts as one -- what we call aliquot. Now it is divided into several aliquots that we can test it to be sure it is the right blood, the right genes and that it is free of infectious agents. That is done and it is stored in the cord blood. When the family decides they want to participate, they give informed consent. The blood is then sent to us. We check to be sure that it is the right blood and that it is free of any infections. The patient comes in we infuse the cord blood. We do a test beforehand to find out how much insulin they are making as a baseline. Then we infuse the cord blood and ask the question down the road what affect this has had on the patient's own insulin production.
Do you have to use the child's own umbilical cord blood?
Dr. Schatz: Yes, absolutely. That's a limitation. It has to be and that is what we call autologous cord blood. Let's say that you had a sister who had a child with diabetes and you gave birth to a child and you just wanted to use that cord. We cannot use it. That would be called an allogeneics system and you would be potentially at risk for graft versus host disease. That may be in the future as we use it with other agents, but right now, that is not an option.
What is the theory about cord blood affects the body?
Dr. Schatz: We had three theories to begin with because we really didn't know. The initial theory was that there was a homing effect. In other words, cord blood cells would come to the pancreas and exert some kind of an affect to cause the pancreas, which is being destroyed, to regenerate. That was the initial theory proposed by Hess in that initial manuscript in Nature Medicine that I had been contacted by the family about. It could be that the cells were going to the pancreas and somehow are medicinal. They are showing, in fact, there is an improvement in insulin production. The other theory is that we know there is a large of number of stem cells in cord blood, which may be capable of differentiating to other cells, like pancreatic insulin producing cells. We have not seen it. We had taken some people and done this and we have not yet seen any evidence of new insulin production so that's the second theory. The third theory is that these cells regulate the immune system; they are immunoregulatory T-cells. Some preliminary data that does suggest that there is an increase and improvement in regulatory T-cells after infusion of these drugs. It appears soon after infusion there is a decrease, but then about six months later there is an improvement in regulatory T-cells. If we believe that type 1 diabetes is a suicide of the pancreas due to a breakdown of tolerance by giving these cells, we could restore some of the tolerance and then lead to an improvement. The problem is, by the time you get diabetes, more than 90 percent of the pancreas has been destroyed so you only have 10 percent remaining. Unless you can also stop that destruction, it is going to be very difficult to try to restore the full function of those cells that make insulin.
I read that a lot of the kids in the study were newly diagnosed so they had some influence.
Dr. Schatz: Those are the people I think will do better, but initially we said it doesn't matter because if we can get insulin cells to be produced by these cells, wouldn't it be nice if we could see people. We have taken some people who have had diabetes as long as five, six years afterwards and asked the question whether we can get them to make insulin. We have not been successful as of yet, but we have also seen these changes in immunoregulation and it does appear that their control is better.
What's the next step for this research?
Dr. Schatz: That is a good question. I think the next step is to really see whether there is an effect. If the data continues to remain promising, we then need a very good control group. That's been initiated. I think the next step then is to do two things. Number one, is to do this in pre-diabetes; those people at very high risk for developing a disease because it is safe. In addition to that, it is my opinion that the cure and prevention of diabetes will not rely on a second therapy, but overall they need multiple therapies. I think we will then need to add safe drugs to this, to not only prevent ongoing destruction of those cells, but also to restore cells. I think we are going to need a cocktail of therapies as has been used in patients, for example with AIDS and leukemia and tuberculosis. We are going to have to apply the same principles to type 1 diabetes.
So the cord blood may just be one part of the whole treatment?
Dr. Schatz: It is one cog in the wheel.
Even though this is preliminary, how exciting is this for you as a researcher and doctor?
Dr. Schatz: It is very exciting. I take care of children with diabetes all the time. I know what it is that they go through. I know what the complications are that they face. Given any preliminary data that is safe and exciting, I'm very excited about it, but again cautious. We have been down too many roads, which we have really believed or thought that we had something and then it turns to nothing. I think that is worse. I think we are honest, we are upfront and very preliminary and cautiously optimistic.
I think its great that a parent called you about this and you listened. You must be really passionate about your work.
Dr. Schatz: I usually listen to everybody. I think I keep an open mind -- we keep an open mind. We, the so called experts, have not been successful in curing diabetes and preventing diabetes. Traditionally we believe in terms of immunoregulatory, immunosuppressant approaches and it hasn't worked. From my perspective, when people call me and they know of something -- most of the time they'll call and I've had many emails regarding all kinds of therapies from throughout the world -- I listen and then at least I'm able to sort of judge whether it has promise. I think there are some promising things. There are some things that I was recently approached about. A family today has a child at risk of getting diabetes. They have a brother with diabetes and this child is likely to get diabetes, but they have been using Juice Plus, which to most physicians and most people in the western world would be some kind of folk medicine. I can tell you this child has not yet developed diabetes and on all accounts should have developed diabetes. There is something there, so my feeling is that I always try to listen to what people have to say and then try and weigh in my opinion, the good, what's reasonable and what is not.
How important is it that we cure this disease?
Dr. Schatz: It is very important. Everyday people die from diabetes. We had a 24-year-old healthy person who had a hypoglycemic -- too much insulin -- seizure and died of the disease not too long ago. It is devastating to the child; devastating to the family. There are acute complications. I have another child in the hospital right now who did not take their insulin and came in a diabetic coma. We are treating that. In relation to blindness, kidney disease, early mortality and the cost to the individual and to society -- it is huge. We have to prevent it. We have to cure it.
END OF INTERVIEW
If you would like more information, please contact:
Desmond Schatz, MD University of Florida Gainesville, FL Melanie Fridl Ross, Public Relations, (532) 273-5812 http://www.ufl.edu
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