Interview with Dr. Melvin Heyman: Tracking Genetic-Based Treatment Options for IBD

Audio Interview:

Listen to an interview with Dr. Melvin Heyman, Chief of Pediatric Gastroenterology at UCSF Benioff Children's Hospital, as he discusses the latest treatment options for Inflammatory Bowel Disease.

Andrew Schorr:

What is the latest, as we look for a road to a cure for inflammatory bowel disease (IBD), Crohn's and colitis, in children? We'll hear from an expert from UCSF Benioff Children's Hospital, next on Patient Power.

Hello and welcome to Patient Power sponsored by UCSF Medical Center. I'm Andrew Schorr.

Inflammatory bowel disease is one of the five most prevalent gastrointestinal disease challenges in the United States. The overall healthcare cost is more than $1.7 billion. Typically, people are diagnosed when they're teenagers or young adults, and of course there is, right now, no standard cure for the condition, and commonly requires a lifetime of care.

Joining us is an expert in the field, Dr. Melvin Heyman. He is chief of Pediatric Gastroenterology at the UCSF Benioff Children's Hospital, and he is also director of the Pediatric IBD program there. Dr. Heyman, welcome to Patient Power.

Dr. Melvin Heyman:

Thank you. It's a pleasure to be participating here.

Andrew Schorr:

All right. First of all, let's just make sure everybody knows what we're defining. When we're talking about IBD we're talking about Crohn's and colitis. Is that right?

Dr. Melvin Heyman:

Yeah, Crohn's disease and ulcerative colitis are the two main forms of inflammatory bowel disease that we refer to. There are other forms of inflammatory bowel disease, but these are the primary forms that we call idiopathic inflammatory bowel disease. In other words, we cannot really define an underlying cause, such as an infection or autoimmune disease, or other type of disorder that can cause similar types of disorders in patients.

IBD Symptoms

Andrew Schorr:

And when they develop, tell us what's going on in the gut and what are the symptoms, and then we'll get to treatment. But help us understand, what are we dealing with, with these conditions?

Dr. Melvin Heyman:

Okay. There are two main types, as you just mentioned, and one is Crohn's disease and the other is ulcerative colitis, and they can present very similarly. It can be difficult to distinguish between the two. Crohn's disease can cause disease anywhere in the gastrointestinal tract, from your mouth right down to your bottom, to the anus. Ulcerative colitis, as its name implies, is limited to the colon, which is the large intestine, therefore there's one situation where ulcerative colitis can be cured, and that's if the colon is taken out. In Crohn's disease that option does not exist.

These diseases can present very similarly. The typical symptoms are abdominal pain, cramping pain, diarrhea and sometimes fever. About 70 to 80 percent of children who have one of these diseases will present with one, two or all three of these symptoms. In ulcerative colitis, about 95 percent of the children will present with red, rectal bleeding. In Crohn's disease, blood may only be seen in about a 20 percent or so of children who have that disease.

In Crohn's disease, there tends also to be involvement in the perianal area in about one third of children, so that can be a hint of what might be going on. In fact, we've had a few children present with severe constipation as their only symptom, because they were having so much discomfort and pain when they were trying to pass a bowel movement into the toilet, that they were just holding on to their stool, and so it was believed they just had constipation. And with a good physical exam, it was discovered that they had bad perianal disease due to underlying Crohn's disease. This is something that physicians really need to pay attention to.

Andrew Schorr:

Dr. Heyman, so you used the term earlier, "idiopathic." Parents are saying, is there something we did, is there some food my child ate, or is there something in the genes of our family? Where is the bad guy in this? What do we know now?

Dr. Melvin Heyman:

Well, the first thing I always tell parents is that there is absolutely nothing that they did that caused it. And I think that's extremely important. Parents should not feel guilty that their child has developed a problem such as this, and we'll deal with it. But, again, there is nothing we know that they've done, for certainty, which could have prevented this from occurring.

Now, that being said, we do know about 20, or even up to 40 percent of very young children do have family histories (siblings, cousins, parents or aunts and uncles) who may also have either ulcerative colitis or Crohn's disease, one of the inflammatory bowel diseases, and so we do know that these diseases run in families.

Given that information, there have been many studies since the 80s that have tried to look for genes. There was a marker in the early 80s discovered called HLA B27. This was one of the first genetic markers that actually showed familial tendencies, in that some family members would also have the same marker in their blood. As time went on, we became more sophisticated, and now with the genome project, are actually able to investigate the entire chromosome in people, and in fact, in the inflammatory bowel diseases there have been a number of studies over the past 10 to 15 years that have been able to describe, now, over 160 genes that are linked either to Crohn's disease or ulcerative colitis.

We've made huge advances in the last, oh, 10 to 15 years showing that there are genetic predispositions and specific genes associated with both of these disorders.

Research and Treatment for IBD

Andrew Schorr:

That brings up the question from any parent, I think, well, if you understand that there are genetic abnormalities that may be connected, can you develop medicines that, kind of, fix the gene in my child? We're all aware of the biologic medicines that have been very powerful, that have been breakthroughs for the treatment for so many people over the last several years, but you have to stay on treatment. But is there a way to turn a genetic switch off? You're at a research center. Where are we in looking into that?

Dr. Melvin Heyman:

Well, let me back up for a second, because one of the research projects that we have done is to look at what factors might predispose somebody with a genetic predisposition. We've done several studies that have looked at various underlying factors, or potential triggers that might cause inflammatory bowel disease in somebody who has a predisposition, because they may have a gene, and these include whether a child is breastfed or bottle fed, early on, whether they have had a severe infection in infancy, whether they're first or second born, whether there were problems during pregnancy, whether they were exposed to certain bugs early in infancy, and so on, and we really haven't come up with any specific factors that relate to causing inflammatory bowel disease.

Given that, now we're left with a lot of genes that we can associate with inflammatory bowel disease, so these are being studied now as potential markers of disease. And one of the first genes that has been investigated, quite thoroughly, is the NOD2 or CARD15 gene, and this has been clearly associated with Crohn's disease, that involves a specific portion of the intestinal tract, the end of the small intestine called the terminal ilium, where people who have this gene, and have Crohn's disease, will get more stricturing or penetrating disease, a more severe disease.

Now you start asking, okay, how can we use genetics to help guide treatment? Well, this will give you an example, where, if somebody has this specific gene maybe they need more aggressive treatment early on to help prevent some of these complications from occurring. Where this is all heading is that, what we hope to do is be able to characterize individual patients by a genetic marker that will help guide the future therapy. In other words, if we have gene A in a person with involvement of certain portions of the gastrointestinal tract, maybe drug regimen A will work for that patient, whereas, if somebody has gene B, a different drug regimen, B, if you want to call it that, will work better for that subject.

We're still many years, 15, 20 years away from being able to really direct treatment in this direction, but at least we're starting to think about that. And some of the studies, that we're involved in here at UCSF, are part of these multicenter, national studies that involve thousands of children, where we can get a pretty good, at least beginning, of looking at the natural history of the disease, and then trying to categorize which gene is associated with what outcome in specific patients.

Andrew Schorr:

I understand we're in this age of precision medicine, and you're trying to match the right treatment for the right child, and their biologic situation, to help limit the effect of the disease as best you can, but is there anything you can see in your crystal ball yet, that looks like it could be a road to the cure, or where there's a debate, even where this can get us further down, where the hope that somebody could have less treatment or no treatment, some day?

Dr. Melvin Heyman:

Yeah, that's a complicated question, because what it's asking is, do we have the capability of predicting whether a treatment will cure the disease. I don't know the answer to that, and I don't think anybody could. Our hope is that if we can come up with genes that are causing certain types of defects in the gut, for example, if there's a gene for a specific immune mechanism, involving predisposing certain bacteria to be in the gastrointestinal tract, and there's a little bit of evidence for all of those factors, maybe we can then give something into the body that will turn that gene off.

And the paradigm, I guess right now, is cystic fibrosis, where even though the genetic link was found 25 years ago, they have, just this year, come out with one of the first drugs that specifically is aimed at one of the defects of one of genes that accounts for about 5 percent of the patients. So I think, what we're going to be doing with all the gene studies is categorizing. Right now we have two diseases, inflammatory bowel disease, broken down into ulcerative colitis and Crohn's. Well, we may be able to break that down into 50 different disorders depending on what somebody's genetic makeup is, and then develop specific treatments for each of those disorders. And, I think in the long run, that may help guide better treatments and ultimately, hopefully, a cure for these chronic disorders.

Clinical Trials

Dr. Melvin Heyman:

All right. Well, then the question I think parents, wherever they may be listening, may be saying, and patients of different ages, it sounds like having a relationship with a research center may be a good idea while this research is going on. I mean, what's your view of it, as far as people considering being in trials, etc.?

Dr. Melvin Heyman:

Absolutely. I think that state of the art care is being provided in centers where these studies are going, it's not just looking at genetic markers, and so on, but it really involves the parents and patients from the minute they set foot into our clinical programs, because I think we're oriented towards, first of all, making a relatively quick diagnosis, if inflammatory bowel disease is suspected, and using modern tools. For example, an upper GI x ray used to be one of the tools to diagnose whether somebody has small bowel disease. Now we're using MR Enterography, which involves no radiation to the children, because I think that's important, in the sense that children who start off young, potentially, will be exposed to radiation from each time they go to the emergency room and have a CT scan, or somebody who doesn't know them says I'm going to get an X ray.

I think using better imaging, modern imaging techniques, such as an MR scan, or even now the capsule endoscopy, which just involves swallowing a little pill that has a camera on it, that gets pictures throughout the intestinal tract, are better ways of helping to clarify what is wrong with the child who is having chronic abdominal pain, diarrhea, and so on.

Being involved in multicenter studies, as children, provides a useful way, to more clearly, define what is happening with patients who have inflammatory bowel disease. The disadvantage of studying adults is that they have had many more years of exposure to environmental influences, medications, other diseases, surgeries, and so on, that may have an influence on the outcome of their underlying inflammatory bowel disease, whereas, especially young children, really haven't had these outside influences, and so we can get a much better and clearer picture of what the natural history of disease is.

In some of the studies we're doing, one of 30 or 40 centers, which involve several thousand patients in the pediatric age group each. In fact, one of the studies we're doing, now, is involving children who are diagnosed with inflammatory bowel disease, under the age of two or six, the, so called, very early onset inflammatory bowel disease, which does occur. Roughly 3 percent or so of the patients, who have inflammatory bowel disease, start having disease early on, that early in life. Being involved in these multicenter studies helps identify it.

Research Progress

Andrew Schorr:

Dr. Heyman, your center is devoted to children with these diseases, and as you mentioned, you're helping lead the way in research. From where you sit, where do you think the future is headed, and what hope would you give to either children or teenagers, young adults, and parents who may be coping with this condition now?

Dr. Melvin Heyman:

We are actually now defining certain patients, already, who have disease that can be cured if they have very specific genetic abnormalities. A few years ago, about three or four years ago, an IL 10 receptor defect was found in a group of—actually, in about 10 patients, who presented with severe, what looked like Crohn's disease in infancy, in the first 12 months of life, especially, with perianal fistulas. And these patients were diagnosed with this defect and are cured with bone marrow transplant. That's actually a very exciting development, which now does show how defining somebody's disease, by a genetic defect, might lead to specific cures.

The future is constantly improving for these children. Fifteen, 20 years ago, we had two main drugs that we were using. We've started adding more drugs to our treatment plans, and also better nutritional regimens, and these have all led to much better patient outcomes. Very few of our patients now need to be hospitalized, whereas, in the past we used to have several patients in the hospital at any one time. In fact, I run a camp for children who have inflammatory bowel disease. You can see 100 kids, and 40 counselors, all have inflammatory bowel disease, running around having a great time, all day long, outside in a camp environment.

In the future, what we, again, hope to do, is be able to define certain groups of patients with specific genetic defects, such as the infant group that I mentioned earlier, and if we can better define what the underlying problems are, hopefully find cures or, at least, directed treatments for these different subgroups.

Andrew Schorr:

Well, we want to thank you for your really career long devotion to people, and summer camp, helping with that, as well, and wish you all the best with your research and your devotion in the clinic every day. Thank you so much for being with us, Dr. Melvin Heyman, who is the chief of pediatric gastroenterology at the UCSF Benioff Children's Hospital. Thanks for being with us.

Dr. Melvin Heyman:

My pleasure, and thank you.

Andrew Schorr:

Encouraging news as research continues for children with inflammatory bowel disease. I'm Andrew Schorr. Thanks for being with us. Remember, knowledge can be the best medicine of all.

Please remember the opinions expressed on Patient Power are not necessarily the views of UCSF Medical Center, its medical staff or Patient Power. Our discussions are not a substitute for seeking medical advice or care from your own doctor. That’s how you’ll get care that’s most appropriate for you.

Recorded on: June 25, 2013


Reviewed by health care specialists at UCSF Benioff Children's Hospital.

This information is for educational purposes only and is not intended to replace the advice of your doctor or health care provider. We encourage you to discuss with your doctor any questions or concerns you may have.

Related Information

UCSF Clinics & Centers

Inflammatory Bowel Disease Program
1825 Fourth St., Sixth Floor
San Francisco, CA 94158
Phone: (415) 353-2813
Fax: (415) 476-1343

Condition Information