Announcer: Examining the latest research and telling you about the latest breakthroughs. The Science and Research show is on The Scope.
Interviewer: We're talking with Dr. Steven Guthery, a gastroenterologist that sees some of the toughest medical cases, kids with rare and undiagnosed diseases. Dr. Guthery, can you explain what a rare disease is?
Dr. Steven Guthery: A rare disease has been defined variably. In the United States, it's defined as a disease that occurs in fewer than 200,000 Americans. There are a variety of publications that estimate the number of rare diseases. So there's anywhere from 5,000 and 8,000 rare diseases. These individually can be quite rare but in aggregate, if you take all rare diseases and clump them together, they're actually common as a group.
Interviewer: So what is an example of some of the cases that you see in your clinic?
Dr. Steven Guthery: We see a variety of rare diseases that occur predominantly in the gastrointestinal tract or the liver in children. Examples of this include primary sclerosing cholangitis, which is inflammatory problem of the bile ducts of the liver. We see rare conditions such as biliary atricia, which is malformed bile ducts of the liver in particularly infants. There's an estimate that about 5 per 100,000 children have biliary atricia. That's in comparison to something like coronary artery disease, or heart disease, which occurs in about 6,000 per 100,000 individuals.
Interviewer: Can you give an example of what some of these kids are going through?
Dr. Steven Guthery: As they grow, many of the children have frequent visits to the doctors, frequent hospitalization. Some may require multiple operations. We have patients who occasionally have multi systemic disease so it may not only be their intestine or their liver but it may be their brain, maybe their heart, maybe their lungs, so they may end up traveling from doctor, to doctor, to doctor over time.
Interviewer: What are you researching in this area?
Dr. Steven Guthery: We've been increasingly interested in understanding what's a rare disease. In Utah we have this very unique sort of healthcare system for the kids. The vast majority of children that live in Utah receive their care at Primary Children's by University of Utah physicians. We have the ability to count up the number of children with disorders and then sort of say that's a rare disease, that's not a rare disease. For example, one our trainees, Dr. Mark Dunnell, who's now at the University of Manitoba, was able to establish essentially that disorders that he was interested, which are immune disorders of the liver in children, are rare diseases.
Interviewer: What does that do for you? What can you do with that information?
Dr. Steven Guthery: It opens up the door for a variety of research initiatives, research dollars, maybe even industry interest in the disorder. The Orphan Drug Act was passed in the early 80s. It offered the pharmaceutical industry incentives to develop therapeutic products for rare diseases.
Interviewer: Yeah, I hadn't really thought of that aspect, that you really have to champion these diseases to get the support to help these people.
Dr. Steven Guthery: Everything we learn about ulcerative colitis in children we learned in adults. The number of adults overwhelm the number of children. Policies are driven towards those adults. Healthcare plans are driven towards those adults. Drug development is geared towards those adults with the condition. So you do have to champion the subset of children that have it.
Interviewer: So what's an example of that?
Dr. Steven Guthery: For adults, 13 and above, they can swallow a pill. A child may not be able to swallow a pill. In order to get that medicine to them they have to either open it up and sprinkle it on some pudding and it may only a single product that you're able to open up. Well, that particular product may not be covered by the child's healthcare insurance or it may need to be compounded and for some reason it's extraordinarily expensive or complicated to compound it into a suspension so the child can take it. So we end up having to jump through a variety of bureaucratic hoops just get the medicine that the child needs.
Interviewer: You also see patients who have undiagnosed diseases whose disease defies category. What can you do for them?
Dr. Steven Guthery: Some patients that have undiagnosed diseases actually have a diagnosable condition. It just takes them awhile to arrive at that diagnosis and there are a variety of factors that can contribute to that delay. There's a subset of patients and I think that, particularly in pediatrics where there's a lot of patients that are being referred in, many of us encounter patients that have no known diagnosis. For those patients, we're beginning to study them in terms of, especially if it appears as if they have a genetic illness before genome sequencing, for example. But there are other newer technologies that undiagnosed diseased patients can have access to in a research setting.
Interviewer: Have you used whole genome sequencing to solve an undiagnosed disease?
Dr. Steven Guthery: Sometimes a disease is so rare that only one person exists, and if I talk too much about it it's identifiable. I can give an example without giving too much detail. We have a patient that several of us took care of that had multi system disease and lived for 10 or 12 without a diagnosis and the treatment was actually successful. They appear to now have maybe even a cure. Then now we go back in time and say, well, can we make a diagnosis here? We used whole genome sequencing on a research basis and were able to identify the cause of this child's condition.
Interviewer: Oh, really? So you found the disease that they had.
Dr. Steven Guthery: When you do these experiments you find tens, if not hundreds, of genetic changes. You have to use intuition, science, and informatics to whittle that list down to try to be able to test the hypothesis that that genetic change is causing the child's illness. A variety of things happen, including another group published the same mutation in another child in Japan. The mutation occurred in a gene that we know, when you have mutations in that gene, you can get human disease. So that was another piece of evidence.
Interviewer: Now that you have that mutation, can that be put in the body of knowledge?
Dr. Steven Guthery: This is technically a patient that had an undiagnosed disease and has subsequently sort of has a new disease. It's a process that really drives scientific discovery. One thing, from the care side of things, is can you design, for a patient that has multi system, a new healthcare delivery method.
For example, you have a patient that has multi system disease. This patient had three systems. They're going to see three or maybe even four doctors. That's hard. Not only is there uncertainty but you have to make appointments to see them and maybe, if they live far away, they may have to come down and see one doctor one day and the next doctor three days later. So trying to coordinate care can be a challenge. So can you develop new ways of delivering more efficient care for those patients? That's one sort of thing that we learn from just a single experiment. That's not rocket science. It just became very apparent that if you can bring people together at one time just to look at a patient then it really improves the patient's care.
Interviewer: Right.
Dr. Steven Guthery: If they have a new disease then suddenly you have the ability to take the information and put it into the body of knowledge. Specifically, if this particular patient had a mutation in a gene that may be important to a more common illness, and so can you generalize that finding to the more common illness and find out if that gene's pathway is important in the disease? We also use that information to help develop new bioinformatic tools to go through genomic data. So just that one experiment drove sort of thinking on how we deliver care. It drove maybe a new biologic process that's important to more common disease and it also drove the assistance with the development of newer technologies sort of in this realm of genomic medicine.
Interviewer: How do you think treatment for rare disease might change in the next 10 or 15 years?
Dr. Steven Guthery: I've been thinking of this analogy about Southwest Airlines and how they move lots of people from city to city. Because of the volume of passengers moving from Salt Lake to Denver they are an infrastructure to be able to move those passengers quite efficiently. That analogy serves for healthcare. For example, many of our processes or treatments are geared towards common illnesses, but for patients with rare diseases it's sort of like there are two to three passengers in rural West Virginia that may need to get to rural Montana. There's no efficiencies or good systems to move patients from small town to small town.
Interviewer: So what can you do for those two people?
Dr. Steven Guthery: They need a Learjet and somebody has to be willing to pay for the Learjet.
Interviewer: Yeah. Well, how do you design a Learjet for rare disease patients?
Dr. Steven Guthery: I think that the first important thing is to understand that those patients are fundamentally different. Patients, families, and physicians must advocate for those patients that have rare disease. They must be advocates not only in developing new research treatments, developing new science, but they also must be advocates for themselves, for their family members, or for their patients to navigate the healthcare system. They almost have to be sort of taken out of the machine and put into a specialty care center. It's not Walmart, it's the neighborhood boutique.
Announcer: Interesting, informative, and all in the name of better health. This is The Scope Health Sciences Radio.
