Tracking Developments In Diabetes Research

Scientists report that they have been able to selectively kill the defective autoimmune cells that were destroying insulin-producing islets in samples of human blood. Denise Faustman, director of immunobiology at Massachusetts General Hospital East, describes the latest diabetes research.

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IRA FLATOW, host:

This is Talk of the Nation: Science Friday, I'm Ira Flatow. Back in 2001, we began following the work of diabetes researcher Dr. Denise Faustman at Harvard. Back then, Dr. Faustman was reporting that she could cure type 1 diabetes in mice, by stopping certain immune cells from attacking the cells in the pancreas that make insulin.

And once these immune cells were disarmed, the mouse pancreas actually regenerated, and blood sugar levels returned to normal. Well, that was great news if you are a diabetic mouse, but we're of course more interested in curing the disease in humans. Well, it's seven years later now, and the first clinical trials in humans are now underway, and she's here to tell us about it.

Dr. Faustman, the director of immunobiology at Mass General Hospital East, associate professor of medicine at Harvard Med School. Her research is being reported in the proceedings of the National Academy of Scientist. Welcome back to Science Friday, Dr. Faustman.

Dr. DENISE FAUSTMAN (Director of Immunobiology, Mass General Hospital East; Associate Professor of Medicine, Harvard Med School): Well, thank you for having me. It's always a pleasure.

FLATOW: You're welcome. Give us a little bit - let's cover the background a little bit about the mice first.

Dr. FAUSTMAN: Well, as you said, we have a lot of happy mice, so.

(Soundbite of laughter)

Dr. FAUSTMAN: That's the bottom line. The concept that you presented a minute or two ago, was the concept that prior to our work in 2001, it was thought that if you were a mouse and you had end stage type 1 diabetes, that's the autoimmune version of diabetes, there were few versions for disease reversal.

So, with a lot of hard work over many years, we found two drugs that could specifically in the mouse kill the bad white blood cells, and as you mentioned, we had a very nice surprise in those experiments, in that we thought we were going to need islet transplants, but the animals did something very unexpected. And that was once the disease was removed, the bad white blood cells, the pancreas regrouped.

FLATOW: Hmm. And you postulated that there were possibly stem cells growing around that came back to the pancreas and regrew new cells.

Dr. FAUSTMAN: Yes, yes. We - of course in those papers in 2001 and then in Science in 2003, couldn't explain all the cells...

FLATOW: Yeah.

Dr. FAUSTMAN: That might contribute to the regeneration. There appeared to be regeneration that was just spontaneous, and we could also boost the regeneration in a faster way...

FLATOW: Mm.

Dr. FAUSTMAN: By using a stem cell we identified in the spleen as well.

FLATOW: Mm. So, now takes us to the human side. Where are we in the human side of this now?

Dr. FAUSTMAN: Well, that's a new data that came out today in PNAS, a major medical journal. And the new data suggests that these rouge T-cells, bad white blood cells that were in the mouse we can also find in humans with type 1 diabetes, as well as some other human autoimmune diseases. Not only can we find them, but in culture, we can kill them in the same way.

So, this means that there's a greater chance that we can start to translate these therapies...

FLATOW: Mm.

Dr. FAUSTMAN: With a logical process instead of just hoping, humans have the same mechanisms (unintelligible) 10:00 that the mouse did.

FLATOW: And how do you go about killing these bad white blood cells?

Dr. FAUSTMAN: Oh, that's kind of the fun part of this project, because we're using a vaccine that's been out there for about eight years, and the vaccine's called BCG. And in the rest of the world, outside of the United States, it's a mandatory vaccine, once or twice or even sometimes multiple times, to prevent TB.

And in the U.S., it's used for cancer, and the reason we're interested in that vaccine, is it induces something in your body called TNF, Tumor Necrosis Factor. And we think the way to kill one population of this rouge T cells, whether you're a mouse or whether you're human, is with TNF.

FLATOW: Mm-hm. And so you're trying that out in humans now?

Dr. FAUSTMAN: Yes, yes. So, in the time that you followed our work, from 2001 to now, we're actually in human clinical trial. So, we're not sure if the humans are going to be as happy as this mice, we're very early in the process of testing it. But the phase one trials are ongoing here in Boston.

FLATOW: So this is a drug that's already available, we don't need to make a new drug?

Dr. FAUSTMAN: Yes, yes. Well, it's available, probably in the wrong dose and the wrong size...

FLATOW: Mm.

Dr. FAUSTMAN: And the wrong bile. But we did not need to spend the cost for manufacturing or primate testing. It's something that we know it's manufactured in a safe version.

FLATOW: Mm-hm. And you say, when - well, let's find out, when will you think you know whether it's working in humans or not? How much time has to go by?

Dr. FAUSTMAN: Yeah. So, the trial started in January 2008, and these are phase-1 clinical trials...

FLATOW: Right.

Dr. FAUSTMAN: Meaning, you're giving itsy-bitsy tiny doses. But why these trials are unique in the field, is that we're giving these itsy-bitsy, tiny doses of vaccine in people who already have diabetes to reverse it, and we're checking out the safety.

FLATOW: Mm.

Dr. FAUSTMAN: Now, you might say why do you need to check out the safety if four billion doses have been given to the world.

FLATOW: Yeah.

Dr. FAUSTMAN: Well, you know, if the FDA says check out safety, you check out safety. But the added bonus is all these new blood tests that we're working on to track these bad t cells are being validated in the phase-1 trial. So, we'll have that beautiful testing validated by the time we start a phase-2 trial in about 18 months.

FLATOW: What's interesting also is that you mentioned that other autoimmune diseases might have the same mechanism here.

Dr. FAUSTMAN: Yeah, yeah. Yeah, so as you know, and probably most of your people that watch and listen to your show, is that type 1 diabetes is a subpart of a bigger class of diseases called autoimmune diseases.

And they come in all sorts of varieties from lupus to rheumatoid arthritis, to multiple sclerosis, to Sjogren's, and our new data shows that these rouge T cells that we can now kill in culture, extends to work probably in Sjogren's disease

FLATOW: Mm.

Dr. FAUSTMAN: And lupus and multiple sclerosis.

FLATOW: Mm-hm. If this drug is given four billion doses, as you say

Dr. FAUSTMAN: Yeah.

FLATOW: Could you not do a retrospective study and say...

Dr. FAUSTMAN: Oh, yeah.

FLATOW: If there were fewer cases of diabetes here.

Dr. FAUSTMAN: Well, that's actually the data that exists out there already, that suggested the case. There was data reported in Scotland almost two years ago that with the discontinuation of the BCG vaccine in countries in Europe, there was a huge rise in the incidence of type 1 diabetes. And there's also epidemiology data out there suggesting - remember BCG is a version of a bacteria that in a bad form can cause TB.

But what's known worldwide is in populations with high incidence of TB that have high TNF levels, they have almost no autoimmune disease. So, the epidemiology data is already out there and supported this...

FLATOW: Wow.

Dr. FAUSTMAN: But that doesn't mean you know the magic dose, and the magic formula, and the magic group.

FLATOW: I want to ask you to comment - I know it's not your work - but I'd like you to comment on a paper also in this week's Nature that shows that cells in the pancreas can be changed into islet cells...

Dr. FAUSTMAN: Yes, yes.

FLATOW: Restoring their function.

Dr. FAUSTMAN: Yes, so the world evolved a lot since 2001. Remember in 2001, the word regeneration was kind of the R word that you weren't allowed to use.

FLATOW: Yeah.

Dr. FAUSTMAN: Now, we're seven years later, and it turns out there's going to probably be many, many ways to make new islet cells which is absolutely fantastic. So, there appears to be ways in which maybe acshican(ph) cells now and this new paper can go into influence to treating cells.

There's published data that people can coax liver cells into islet cells, probably four or five papers along those lines. There's groups that over the last 10 years have thought duct cells, ducts at the pancreas, can turn into beta cells.

FLATOW: Mm-hm.

Dr. FAUSTMAN: So, the good news is it looks like, at least scientifically, we can make lots of islets, but just keep in mind, if you're making those influence at creating cells from whatever favorite cell you start with, if you put them into a type-1, diabetic animal or type-1, diabetic human and they have this rogue T cells, the disease will reoccur.

FLATOW: It's going to come back because you haven't gotten to the root cause.

Dr. FAUSTMAN: That's right. That's right, and that's happened in the clinical trials for both pancreas transplantation...

FLATOW: Mm.

Dr. FAUSTMAN: And islet transplantation. You put new cells in and the disease reoccurs.

FLATOW: Right. Do these rogue T cells have a genetic signature that you could find them?

Dr. FAUSTMAN: Yeah. We're using specific ways, that's what we're partly reporting in this paper that came out today. Partly the fact that we can now get from a tube of blood from people, a really representation of the T cells by actually using magnets...

FLATOW: Mm.

Dr. FAUSTMAN: A new technology to isolate T cells from blood, and not only can we get those good T cells, but now we can sometimes even identify the specific autoreactive cell to like a fragment of insulin.

FLATOW: So, could you tell in advance before someone develops diabetes that they might be prone to it, because they have these kinds of T cells.

Dr. FAUSTMAN: Yes, we don't that specific work, but many people worldwide, by using genetic T-cell markers and something called autoantibodies can predict with, you know, fairly good accuracy over the last 10 years, who might get diabetes. But up until this time, there's been little options for treatment. If you knew junior...

FLATOW: Yeah.

Dr. FAUSTMAN: Your kid was going to get diabetes.

FLATOW: Do you think now that your work is being published and doctors around the world are looking at it, that they might just go ahead and since this drug is available in the open market, just prescribe it to people with type 1 diabetes?

Dr. FAUSTMAN: Yeah. You kind of worry about that, because it kind of reminds me of people trying to dose insulin without being able to check a blood sugar.

FLATOW: Mm-hm.

Dr. FAUSTMAN: Like most drugs that are out there, the whole secret is not the drug, it's the dosing, and the whole secret of the dosing is having the blood test.

FLATOW: Yeah.

Dr. FAUSTMAN: So, people had tried BCG in the past in humans about 20 years ago, and there was an Israeli group that said they cured one person, and then there were three groups that said it didn't work. But it was kind of like doing a trial with insulin, without being able to check a blood sugar. You really need to know what you're doing and what you're doing fast.

FLATOW: Mm-hm. Give us the road map of how - you know, when do you go from phase one to two to three, things like...

Dr. FAUSTMAN: Oh. OK. So there's two - three goals. One is we'll get through phase one, we're pretty much on target for a deadline, for enrollment and all the T cell monitoring probably in 18 months. And then, phase two, we'll start with - we've got to raise the money for phase two...

FLATOW: What do you mean you have to raise the money?

Dr. FAUSTMAN: Yeah. Yeah. Yeah, that's a good question. It's kind of like working for NPR, you guys have to raise money like you...

FLATOW: Oh, tell me about it.

(Soundbite of laughter)

Dr. FAUSTMAN: We have to raise money too. This is a generic drug. OK? So, the beauty of this program is it's supported by the public. So, public donations come in to try to get this type of disease-reversal therapy tested in human.

FLATOW: Mm-hm.

Dr. FAUSTMAN: And so, as we raise money for phase two, and get FDA approval - these are all double-blinded-placebo-control trials, you know...

FLATOW: Yeah. Well...

Dr. FAUSTMAN: Just like big companies would do, because we think that there's no sense in doing a trial over, to not do it in the proper way.

FLATOW: Mm-hm.

Dr. FAUSTMAN: All these trials are being done properly.

FLATOW: Well, I want to thank you, Dr. Faustman. Maybe some folks listening will send some funding your way.

Dr. FAUSTMAN: Well, we hope. And funding to you, too.

FLATOW: Well, we certainly need it. Thank you very much

Dr. FAUSTMAN: OK. We both need it, right?

FLATOW: All right. Dr. Denise Faustman, director of immunobiology, the Mass. General Hospital East and associate professor of medicine at Harvard Med School. We'll take a short break. Change cues and come back and talk about vaccinations. Don't go away. I'm Ira Flatow. This is Talk of the Nation: Science Friday from NPR News.

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