Are new treatments for celiac disease on the horizon?

More than 3 million Americans suffer from celiac disease, an illness with no current treatment. Is help on the way?

Speaker names marked ? are inferred from speaking time and the show’s known hosts — they are not voice-verified.

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• 0:47Ira Flatow?

  Hey, it's Ira, and you're listening to Science Friday. About 3 million Americans live with celiac disease, a painful immune reaction to gluten. Just a bite of pizza or a chocolate chip cookie can make celiac sufferers double over in pain or send them running for the restroom. In severe cases, celiac can lead to anemia and osteoporosis, and even ulcers and holes in the intestine. But there are a bunch of new drugs on the horizon that offer hope. Here to talk with me about all of this is Dr. Maureen Leonard. She is the Clinical Director of the Center for Celiac Research and Treatment at Mass General Hospital for Children.

• 1:30Ira Flatow?

  She is also an Associate Professor of Pediatrics at Harvard Medical School. Welcome to Science Friday.

• 1:37Speaker 04

  Thanks so much for having me.

• 1:39Ira Flatow?

  Nice to have you. Before we get into the treatments, I think we need to go into some ABCs about celiac disease. Tell us what causes it.

• 1:48Speaker 04

  So, celiac disease is a systemic immune-mediated disorder that occurs in individuals with compatible genetics, and it's driven by the ingestion of gluten. When someone with celiac disease eats gluten, the gluten, which cannot be digested by anyone, can move across the small intestine and interact with the immune cells there to cause inflammation and ultimately, small intestinal damage.

• 2:16Ira Flatow?

  So it actually attacks the small intestines, right? It's attacking its own body?

• 2:20Speaker 04

  Yes, I think the simpler way to describe it is that no one can completely digest gluten, and so there are different proteins that sort of move through the small intestine. It induces increased permeability in the intestine. It allows it to pass through where it can communicate with the immune system.

• 2:43Ira Flatow?

  So it sort of leaks through?

• 2:45Speaker 04

  It leaks through, and then the immune system, in the setting of the right genetics and the right environment, it causes an inflammatory cascade.

• 2:56Ira Flatow?

  Interesting. Now, you said earlier that it just happens, it springs on people, or it can show up any time in life, and do we know why that is?

• 3:06Speaker 04

  So that is a really interesting piece of celiac disease. It literally, it can turn on at any time, and we don't know what those triggers are. So there's a lot of hypotheses about, is it the, how much gluten someone is exposed to? Is it because you're exposed to a virus at a certain time? Is it the use of antibiotics? Is it a change in your microbiome? I think what we can say is that it's not going to be just one thing for everybody. It's probably a combination of factors that ultimately leads to celiac disease being turned on.

• 3:43Ira Flatow?

  Let's talk about some of these potential new treatments in development, because there seem to be quite a few. Let me ask about first, this new drug being tested called TeV408. What is that?

• 3:58Speaker 04

  That is an agent that is essentially an IL-15 monoclonal antibody. And so this is further down in the pathophysiological pathway for celiac disease, where we've already had the gluten seeped through, it's already presented to the immune system, and now it's aiming to block some of the inflammatory cascade, specifically IL-15.

• 4:25Ira Flatow?

  And it's in a Phase II clinical trials on, what, a few people, something like 50? And it seems to have some effect?

• 4:32Speaker 04

  Yeah, so for this, what they did was, they gave this medication to patients with celiac disease, or placebo. And then two weeks later, they put them on what we call a gluten challenge, where they give patients with celiac disease a certain amount of gluten every day, and they did it for six weeks here. And what they saw is that the intestine got worse in people who didn't get the medication, and it stayed about the same in patients who did. And then they saw some improvements in sort of the white blood cells and the other inflammatory cells that were around there, showing that if people with celiac disease are given gluten, this medication can protect against the worsening of the intestinal damage.

• 5:14Ira Flatow?

  Sounds pretty hopeful.

• 5:15Speaker 04

  Yeah, there's been a lot of, I think, really hopeful therapeutics coming through the pipeline. In celiac disease, this is still all new, right? We don't have a therapeutic that's been approved. So we're still, I think, learning as a community about the best way to do these clinical trials and measure the symptoms and how the intestine looks. But there's been so much progress, and certainly, I'm really hopeful that we will have a medication in the near future.

• 5:47Ira Flatow?

  Can you call up another one that you're hopeful about?

• 5:51Speaker 04

  So the medications that are under development, I mean, there's enzymes that are trying to digest the gluten before it gets to the small intestine, so it can't even interact with the small intestine. There's a medication that's aiming to block the increased intestinal permeability, so it can't get through and talk to the immune system. And then there's the TeV, and there's other CD122 molecules that are aiming to really block the inflammation through different cytokines or chemicals.

• 6:28Ira Flatow?

  Now, I know you've said that we really don't know why it just jumps out sometime during people's lifetimes. I understand that you're involved in a study to try to figure that out, correct?

• 6:42Speaker 04

  Correct. So I've spent now over 12 years building and following a birth cohort of infants, over 600 infants born to families with celiac disease, so they have to have a parent or sibling with celiac disease. And so what we've done is, we have followed them from birth through age five. We collect blood every six months where we test for celiac disease. We collect stool, so we can look at the microbiome, and we collect a lot of information about what they're eating, what their environment is like, who's in their home, things like that.

• 7:21Speaker 04

  And our goal is really to understand what factors, environmental, again, from the microbiome and other things, might tip someone towards losing tolerance to gluten and developing celiac disease. And so we have more than 50 children that have developed celiac disease. And so what we're doing now is, we're starting to put some of the pieces together. So we've already published work showing that actually, the microbiome, the stool microbiome in these kids that go on to develop celiac disease, changes two years before they actually have a, before they lose tolerance to gluten.

• 8:04Speaker 04

  We found that kids that go on to develop celiac disease have an increase in intestinal permeability about a year and a half before they lose tolerance to gluten. And we've seen now that there's changes in their metabolome, so the metabolites that are in the stool, really, really early on. So what we're working on now is, we're trying to look at how the immune system develops in their blood, we're looking at what viruses they're exposed to, and we're really building and collecting different pieces of the puzzle to eventually put them all together and try to figure out what markers or what changes we can see years before celiac disease onset,

• 8:47Speaker 04

  so we can eventually try to identify ways to prevent it.

• 8:53Ira Flatow?

  You know, so many people listening to this suffer from celiac, and they're going to want to know, when is this stuff going to be in my doctor's office? And we always tell them, we really don't know, and I guess in this case, that would be the same.

• 9:07Speaker 04

  Yeah, in this case, we really don't know. I think it may take even a little bit longer, because we've never had a therapeutic, we've never had a medication for celiac disease. This might change how we follow patients with celiac disease as well. I mean, a lot of patients with celiac disease aren't followed by their gastroenterologists because they're on a gluten-free diet. And so, once we have alternative treatments, this will definitely change how we manage celiac disease, how we follow celiac disease. But I will say, it is very important that patients with celiac disease get an accurate diagnosis. That can be made through blood tests and biopsy and with a gastroenterologist, but it's very

• 9:48Speaker 04

  important, because as we get closer to medications, people are going to have to have a confirmed diagnosis in order to benefit and potentially take some of these medications.

• 9:59Ira Flatow?

  If a member of your family does come down with celiac, should you get tested also, since it's genetic?

• 10:07Speaker 04

  Yes, we suggest that first-degree family members of patients with celiac disease be tested for celiac disease with the blood test, which is the tissue transglutaminase test. And the most important thing to remember is that you have to be eating gluten for any of these tests to be accurate. Because if you have celiac disease, once you take gluten out of your diet, the symptoms should get better, the blood tests go back to normal, and the intestine will heal, for most people.

• 10:35Ira Flatow?

  That's great. You know, just peripherally, I bake bread, I bake sourdough bread. And I was learning about, there's the original grains of wheat that were discovered, not the stuff we have today, were very low in gluten. And I just thought that was interesting. Maybe people digested it a lot better, because there was no, really low amounts of gluten in that wheat.

• 11:00Speaker 04

  Yeah, it's interesting, in our prospective birth cohort, half of our cohort is from Italy, and the other half is from the United States. So we're looking at differences in gluten intake and timing and all of those things. But the studies in young children do show that large amounts of gluten ingested in early life might increase the risk of celiac disease.

• 11:27Ira Flatow?

  That's called white bread. Yeah. We've run out of time, Dr. Leonard. Thank you for taking the time to be with us today.

• 11:35Speaker 04

  Thanks for having me.

• 11:37Ira Flatow?

  Dr. Maureen Leonard is the Clinical Director of the Center for Celiac Research and Treatment at Mass General Hospital for Children. She's also an Associate Professor of Pediatrics at Harvard Med School.

• 11:59Ira Flatow?

  This episode was produced by Annette Heist. Thanks for listening. We'll see you next time. I'm Ira Flatow.