Jim Evans, MD, PhD, Bryson Distinguished Professor, Genetics and Medicine, UNC Chapel Hill, talks about genetic research being done to help in the treatment of patients with particular DNA-related conditions.
Interview conducted by Ivanhoe Broadcast News in October 2017.
Talk to us about how this came about, were you deep into your genetic research or was it that you were looking to help people?
Dr. Evans: How this story came to be was we were fortunate enough about five years ago to get funding from the National Institutes of Health to investigate how we could use some of the emerging and brand new technologies in DNA analysis and DNA sequencing to benefit patients. For the last five to ten years the field has been gaining a lot of fundamental insights into biology, health, and disease from our ability to analyze DNA. But that technology had not really been translated into patient care. And that’s what we were really interested in doing to figure out how can we use this technology to benefit patients. So we began a study in which we were asking for participants who had been through the “medical odyssey” if you will, trying to get diagnosed, to achieve a diagnosis with their disease and have been unsuccessful. We accrued a group of well over six hundred people who the one thing they shared was that they had a disease that appeared to likely be genetic and yet nobody could explain it and since diagnosis is so critical in caring for people and guiding their care, this seemed like a very promising avenue. Well Ms. Davis was one of those participants and she had been diagnosed many years ago when she was about six years of age with a hereditary movement disorder that had left her using crutches and a wheelchair to get around. In addition she was subject to very painful episodes of muscle and limb spasms every day. When we analyzed her DNA we were very intrigued to see a very particular change in a gene called the GTP cyclohydrolase 1 gene. And that gene had been described in the past as associated with a condition that might respond to a medication called dopa. We were particularly excited to see this because dopa is a commonly used medication. It’s used by millions of people each year because it’s a first line treatment for Parkinson’s disease. So we called Elizabeth’s neurologist and told her about the findings and we all agreed that a trial of this medication, L-dopa, would be worthwhile for Ms. Davis and the results exceeded our expectations. We were absolutely delighted with her dramatic response. She can now walk without crutches she doesn’t have these painful episodes, it was really a wonderful story and it’s the kind of story that reinforces why we engage in patient care and research. Because once in a while you can hit a homerun and it really affects somebody’s life. I would hasten to add that this is not the norm, but when we are able through these new technologies to come up with answers for people that’s a good thing. It has good outcomes and benefits. Elizabeth was definitely on the end of the spectrum where those outcomes and those results were just wonderful. What we hope is that it demonstrates the kind of power that we can sometimes get in the research world; why research is important. Hopefully it’s an indication of things to come, that in the future we’ll be able to make more and more diagnoses that have dramatic beneficial effects for people.
It truly is an amazing story especially when it comes to Ms. Davis. Is there a great number of people out there who are undiagnosed?
Dr. Evans: I would say that there are considerable numbers of people but I would also emphasize that there’s much more to human disease than genetics right? People get diseases for all kinds of reasons and although genetics plays a role in most diseases, it is the driving force in the minority of diseases. The benefits from research like this cross a whole spectrum, a whole range. There are people who will immediately benefit like Ms. Davis, there are also advances that will be made ten years from now, twenty years from now that will benefit all of us because, for example, of the genetic component of disease in general. I think an important message for people is that science is our best hope for realizing gains, treatment, and reducing human suffering. And the timeline for that can be quite variable. Some people will be helped, a minority of people will be helped immediately, but we will all benefit in the long run as we learn more about these diseases.
How does the process work as far as say with the NC gene study, how did it work you said you recruited a certain number of patients?
Dr. Evans: Yeah we did that recruitment through physicians who were seeing people who were mysteries, who were enigmas, and where there was reason to think that genetic analysis might shed light. The second phase of this study which we’ve been again fortunate enough to get funding for from the National Institutes of Health is being run by my colleague Jonathan Bird. And in that study we’ll be investigating whether the routine provision of some of these types of DNA analysis technologies will increase our ability to benefit people in the system. So they will be slightly different types of ways in which we work with those people.
And this is all done in the lab?
Dr. Evans: Yeah, this kind of research really shows how important a multidisciplinary approach is. The function of the physicans and the genetic counselors that are right in the front lines, seeing patients, are crucial to identifying the people who might benefit from this kind of analysis. Then the people behind the scenes in the laboratory who are doing that analysis extending to the people who do the computer and informatics processing to sort through the hundreds of thousands of variants we get when we sequence all of somebody’s genes to try to make sense of that. So it’s the kind of effort that is the farthest thing from the lone wolf in the lab at night you know having a eureka moment. It really shows the eminence power and the need for teamwork. We need everybody from the clinician, the genetic counselor, to the clinical laboratory and to the computer experts to make sense of these kinds of things and make progress.
Does it all come down to, and I know you’re saying not everything is based on genetics?
Dr. Evans: Right. But for some people it can, it does come down to genetics right? Most of us, the ills that we will suffer have something to do with genetics and the more genetic knowledge we find out the better off we will be in the long run. Some people have diseases that are exclusively genetic; that are really driven by genetics and it’s those people that represent in some ways the low hanging fruit for application of these technologies. Ms. Davis was one of those individuals who has a condition that is really dictated almost exclusively by genetics and therefore genetic insight was really primed and poised to make a big difference in her life.
Without that truth be told she may still not ever have know or ever received proper treatment?
Dr. Evans: It was so lucky that we were able to have her in our study because we were able to give her life changing information. And that’s what of course we want for everybody. In her it really worked out wonderfully. And again I see her as a hopeful sign of what we strive for in the future with research in general. It’s the kind of moment that you spend a whole career in research hoping to see.
Especially like you’re saying the application of it.
Dr. Evans: Right. And as both a scientist and a physician I see both ends of that spectrum. Knowledge is important for its own sake and knowledge; it is the thing that will improve our lives going forward over the years. But it’s also as a physician incredibly gratifying to see that knowledge tangibly put to use and helping somebody, and improving their life is very exciting.
The second part of the study does this involve recruiting as well?
Dr. Evans: Yeah. The second part of the study is being headed up by my colleagues Jonathan Burg and Bradford Paolo and the patients will be recruited in a somewhat different way. They will generally be people in whom there’s some suspicion, there’s some type of genetic disorder. And we will be looking to see whether applying this technique of whole exosome sequencing, basically analyzing, sequencing all of somebody’s genes provides a benefit in terms of patient care if that is applied routinely.
And when you read a person’s genes does that tell you the whole story?
Dr. Evans: It doesn’t really for two reasons. One reason is because we’re not very good at reading people’s genes. Even in 2017 while we can sequence your genes and we can discern some things from them, there is so much we need to learn. In many ways it’s like a set of encyclopedias and we can only read every tenth sentence or every fiftieth word. We’re in the early stages of figuring all this out; I would say that we have a long way to go. And the other reason that it doesn’t tell us everything about somebody is that we consist of more than our genes. Our genes are important but they’re not the whole story. We are the product of genetics, of environment and upbringing, of pure chance. So even come that far off day when we really can read your genome with great confidence and know what it means there will still be uncertainty because genetics doesn’t rule our life.
So still a long way to go, a lot more to learn and if people were interested in trying to get involved or find out if they are ….
Dr. Evans: Right. Well I think that probably the best thing for people to do if they’re interested in seeing whether their disease might be genetic, whether these new technologies might benefit them would be to contact a medical genetics team. Probably the best way to do that is to either go to the website of the American College of Medical Genetics and Genomics, which I believe is ACMB.org. Or go to the website of the National Society for Genetic Counselors. I work with a lot of genetic counselors. Either of those websites could tell you about a team near you that might be doing this kind of work, might be doing this kind of research and could certainly guide one to the types of opportunities that might be of interest or benefit to them.
END OF INTERVIEW
This information is intended for additional research purposes only. It is not to be used as a prescription or advice from Ivanhoe Broadcast News, Inc. or any medical professional interviewed. Ivanhoe Broadcast News, Inc. assumes no responsibility for the depth or accuracy of physician statements. Procedures or medicines apply to different people and medical factors; always consult your physician on medical matters.
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