Jeffrey Dunn, MD, a clinical neuro-immunologist at Stanford School of Medicine talks about a new oral option for MS patients.

Transcription

1 Say Ahh! The First Oral Treatment for MS Jeffrey Dunn, MD Jeffrey Dunn, MD, a clinical neuro-immunologist at Stanford School of Medicine talks about a new oral option for MS patients. Are you seeing more MS patients now than before and why? Dr. Dunn: I think so. One of the biggest differences has been the patients that we are seeing MS in, traditionally in the past MS has been thought of as a disease of Northern Europeans and Scandinavian those of that sort of ethnic heritage, the Northern European, Scandinavian heritage. As with any autoimmune disease females more than males, three to one ratio. But classically MS has been seen as a disease of Caucasians, light skinned, light eyed, light haired young adults. But increasingly in this area we re seeing that MS affects not just folks of that ethic heritage but those of Indian ethnic heritage, those of Asian ethnic heritage, Hispanic and African American as well. Historically in the past these sort of have been described as nonconventional groups, the not classical case of MS. It s been thought that MS in those individuals, the nonwhite individuals has been rare in the past. In fact we know now that s not true MS affects all races and our ability and our awareness of the frequency with which it s affecting these non-traditional groups is absolutely increasing. There are more white people than Indian or other ethnic people is that the reason that we haven t seen as much? Dr. Dunn: Some of its environmental you know it seems that the risk of developing MS has a lot to do with where you live. And so we see a number of people that for example have been born and grew up in India they never developed MS. They move here and we re diagnosing them with MS. So it could be an environmental factor. The honest truth is we don t know what causes MS so I can t really say it s environmental for sure. Are there more places in America where you see more MS cases? Dr. Dunn: Definitely yes. There is an imaginary line that stretches between New Port News and Santa Cruz it s the thirty seventh parallel in the United States. And if you draw that line and you re north of it your chance of developing MS in your lifetime is significantly higher than if you grew up south of that line. Is that all the way across the border across the country?

2 Dr. Dunn: New Port News to Santa Cruz. We don t know why? Dr. Dunn: We don t know why but we know that if you are born and grow up at the equator your chances of developing MS are negligible. The more north you move away from the equator and in fact the more south you move away from the equator the higher and higher the risk is that you ll develop MS in your lifetime. So for example those living in Calgary, Canada have a much higher risk of developing MS statistically than if you were to grow up in San Diego. How much higher a risk, is there a percentage that you can tell me specifically? Dr. Dunn: Some of the risk it s not fully quantified. In the northern US there are estimates that maybe about one out of eight hundred people could develop MS let s say in and around Seattle, that would be a medically sophisticated area where the numbers are pretty reliable and the research has been consciously done. Let s just take Mexico just as an example; right after World War II it was literally thought that there was not a single case of MS in Mexico, in the entire country. By the nineteen eighties it was thought that there were a few cases maybe three or four out of a hundred thousand people. And even then it was thought that those individuals with MS had European heritage, ethnically, those of mixed ethnic heritage. More recently research now shows that the true incidence of MS in Mexico might be not as high as in the northern United States but maybe one third of what the average incidence rate is in the US overall. The dynamic there is that two generations ago we thought there was no MS in Mexico, one generation ago we thought it was rare but definitely present and now recently it seems very much present in those of mixed ethnic heritage purely Hispanic ethnic heritage at a ratio that s at least one third as high as what we see in the northern US. So why is that, why the increase? Dr. Dunn: Some of it could be just ascertainment and awareness, some of it s a self fulfilling prophecy. If the medical students of Mexico or South American countries or of Asian countries are taught that there is no MS in their country at all and they have a patient walk in to their clinic who has MS they re not going to diagnose MS in that individual because they re going to say, well it can t be MS we don t have any cases like that here. I think that was part of it. I think part of the increasing awareness is the increasing availability of MRI. MRI s are a really sensitive tool for identifying MS because it can really show the brain in real time. And so the MRI can reveal areas of MS that wouldn t have been, you know

3 they re not visible to the naked eye. So I think with MRI becoming more available in this country and then also worldwide there s an increase in recognition that MS is going on. Patient s symptoms may be attributable to MS whereas they may have been attributed to something else in the past. So I don t know what parallel it is actually. So it s a big deal because if you look at a map and if folks grow up around the equator or maybe ten or fifteen degrees latitude north or south their chance of developing MS is low in their lifetime. But you move up to past the thirty seventh parallel north or south and the risk of MS markedly increases. And that s still true to this day as it was when it was first discovered after World War II. Are there any studies that have come out recently about this, about different ethnic groups getting this, are there any studies that have got your interest? Dr. Dunn: Absolutely yes. So in the past we ve thought of MS as one disease but just with a lot of variety between individuals. Now we re at a spot where we have to ask ourselves is MS not one disease is it several. As an example, we ve known, that a type of MS that in the past was called opticospinal MS, more frequent than those of Asian ethnic heritage or those living in Asian countries, those folks didn t appear to respond to a molecule called interferons one of the main treatments we have for MS. Why is that? We ve thought in the past that MS is one disease with a lot of differences just between individuals but now we have to ask ourselves is it not one disease but actually is it many diseases, is MS just a syndrome manifested in multiple different ways. Our scientists here on this campus have recently identified chemicals that seemed to drive the autoimmune response. In some cases they see that a T-cell line called TH-1 which causes a certain elaboration of certain proteins like interleukin one drives the inflammatory response that causes the brain inflammation of MS. But in other cases in other individuals it s not the interleukin one it s a similar but unique molecule called interleukin seventeen mediated by so called TH-17 cells that drive the response. Now if a patient comes in to our clinic we see them their symptoms might be very similar. Let s say we have two different kinds of MS both patients might be describing the same symptoms, both might look alike in a clinical sense but their blood tells a different story. But they may actually have two different subtypes of MS. And what s interesting about this is that there s an early suggestion, it s not conclusive, there s an early suggestion that some of these blood markers predict response to different treatments. So the hope is as we go forward we can individualize medical care. We all know that cases of MS are different we all strive to provide treatment to the individual rather than to the group but how do we do that. We have never previously had a test by which somebody comes in

4 with MS and we say, okay here s MS we re going to draw your blood we re going to find out your specific type of MS how it affects you as an individual. Not just as a group as an individual. And if we know that and learn that down to the molecular level of detail the hope is we can predict which treatment is specifically going to give that person their maximum benefit to allow them to achieve their maximum level of wellbeing. So how many types of MS, I m kind of seeing this as the MS spectrum is that what it would become? Dr. Dunn: Yes. Instead of being a monolith of a disease we think that we may gain more by seeing MS as sort of a spectrum of disease. Now we don t have those fully defined but that s what we re in the process of doing and I think we will have it figured out in this next medical generation. Do you know how many possible types of MS there could be? Dr. Dunn: It s probably more like a handful. If there s a spectrum it may be what s so called conventional multiple sclerosis which overlaps partially with a syndrome that may be opticospinal multiple sclerosis which overlaps with a syndrome that is increasingly known as NMO spectrum disorders which may then evolve or sort of overlap with neuromyelitis optica. And then in between there are a number of different subtypes. There are cases in which people their immune system can attack them once but then never again it s called a clinically isolated symptom. There are cases in which people have multiple attacks in a year and yet other individuals who look just like them only have one attack every five years. So people have said MS is like snowflakes in the sense that there are no two cases that are alike. No two individuals that are alike. My friend has MS and feels like there has been nothing new to really change her life in the last five years is that true? Dr. Dunn: Nothing could be further from the truth. In 1993 and for all years before that there was not one single treatment that was ever shown to have a disease modifying effect. Meaning there was nothing that was shown to actually effect the number of relapses somebody would have or their tendency toward disability as their MS disease moved forward. In 1993 the first medication proven to have some impact on the disease was approved, that was beta serum, but today as I m speaking with you there are eight FDA approved medications for MS. That s happened in the course of less than seventeen years. That s essentially more than one medication for every two years that s new that s been shown to be effective for MS. And not only that but there are five oral medications today at Phase III level of testing in the FDA pipeline. Phase III is the

5 last stage before FDA approval. So these are not pie in the sky ideas these are molecules that have shown significant benefit and significant promise that we can expect I think approval of several of them within the next several years. What are you most excited about, which drugs and what do they do? Dr. Dunn: Different medications work differently so the first oral medication for MS was just approved two weeks ago. And patients are excited about that because it s an oral product, we ve never had that before. What s it called? Dr. Dunn: The brand name is Gilenya, the generic name is fingolimod. What does it do? Dr. Dunn: It prevents lymphocytes from getting out of the lymph tissue in to the brain. The balance of MS that we need to achieve is we need to do what s necessary to prevent the cells from attacking the brain and causing damage to the brain without killing the important effects of the immune system in general. We need our immune system, our immune system is like the body s military. It fights off infection, it prevents cancer cells from taking root, we need our immune system to help protect us as organisms. And yet in MS the immune system can be too strong, it can overact so there s a delicate balance, how do we preserve the health of the immune system to be able to fight off infections and cancer cells and yet not allow the immune system to attack the brain where it can cause damage. And that s what this drug does? Dr. Dunn: So fingolimod works by preventing lymphocytes from getting out of lymph tissue without killing the lymphocyte. It kind of locks them up in the lymph nodes almost like horses in a barn and you shut the door and bar the door. The lymphocytes stay viable but they can t get out of the lymph tissue to attack the brain and if they can t attack the brain the brain can t get inflamed or damaged. Is there another drug that you re excited about? Dr. Dunn: There s also a number of what are called monoclonal antibodies and the nice thing about monoclonal antibodies is that they re really specific in terms of where they affect. Monoclonal antibodies are like smart bombs, they have a very specific target, they hone in on that target and at their best they leave everything else unscathed. So the hope there is that they can be highly effective without causing collateral damage to the immune system. But I think what s both

6 exciting and a real challenge in times to come is we already have eight medications for MS, we have a number of oral medications in the MS pipeline that are pending at Phase III levels and beyond. We have a number of IV medications, monoclonal antibodies pending. We re going to have a library soon of different treatments for MS which with each of these medications working by different mechanisms. Now not every single medication is going to be helpful for every single individual but take those two things I just said first, MS manifest differently in different individual. Second, we have a broad and increasing range of medications that work by different mechanisms. The challenge in the generation ahead is how to match the specific therapy to the specific individual to get maximum affect for the individual and their wellbeing. It s going to be a huge focus of research in this next generation that s where the field of MS is going. Is there any breakthrough when it comes to diagnostics? Dr. Dunn: There s one thing it s interleukin. Let me compare MS for one moment to diabetes, let s say you have a new drug that you want to develop for diabetes and you want to see if it s effective for people. When you give an individual a diabetic medication you can measure their blood sugar right at that time, literally you can determine their average blood sugar over weeks by a single drop of blood. You d be able to tell right away if your medication was helpful. With MS we don t have a blood test we can t tell how people are doing right after their first dose of a medication. So even to this day the measures we use are MRI measures is there more lesion load a year after their diagnosis, a year in to therapy compared to what their baseline was the number of relapses their having and how much disability they may be accumulating. Those are crude measures and we need to do better than that. The tests that our scientists have discovered here isn t conclusive but it offers hope that it can predict subtypes of MS and predict treatment responsiveness. In other words instead of having to guess at what might be the best therapy we can actually preemptively identify what is the best therapy, not for a group but for that specific individual. That s a real breakthrough it s a huge issue. That s the huge challenge so MS affects all these different people in all of these different ways. The data that we ve got kind of talks about how people respond in groups. Like of these four hundred people there was an overall average reduction in relapse of thirty seven percent well that doesn t mean that every single individual has a relapse of thirty seven percent. In fact what s happening is some people aren t responding at all and some people are responding much better than that. So the question is who s going to respond the best to that specific medication? And if you ve got a whole library of different agents working by different mechanisms and you re facing patients with whole different profiles that some are going to respond to different medications

7 differently the ability to predetermine who s going to optimally respond to medication can make a huge impact on that patient s, that individuals quality of life. We see somebody it s like okay you ve got MS we want to treat you we ll take our best shot here s something we think will work. But then if they don t respond, two years later they ve had several attacks and they ve lost some ground we can t make up for them. If we could only predict what s going to be the best medication for them from the very beginning we can change those people s lives. And that s something avidly to be sought and desired. How soon do you think this will become a reality? Dr. Dunn: We re doing it right now. This is what s happening. The setup that we have here allows us to see an individual, the cause and the cure for MS is floating in the bloodstreams of the men and women who have the disease. They have the cause and the cure of MS in their bloodstreams. The patients aren t the problem the problem is that doctor s haven t been able to find the cause and the cure. In the past we ve used animal models like mice research, that s been helpful. But we have an opportunity now, we ll see a patient in clinic if they re having an acute attack we can draw their blood during an acute attack. We can literally walk that sample across the street and have our scientists look at it in terms of its protein profile in a field of what s called proteomics. We can see that same individual a few months later they re in remission. We can draw their blood again, we can get the sample of blood again we can walk it to our scientific colleagues and we can look at the difference in their bloodstreams and their proteins of their blood during an attack and in remission, we can see where the difference lies. No animal model in between, the patient is their own control. If we find differences we can either predict which medication is going to be best for them or we could tailor design a brand new medication that s specific for that individual that can keep their disease in remission. So the interface of having actual human tissue in real time studied by state of the art immunodiagnostic technology is the field of what s called translational research and that s what we re doing here. I think it offers tremendous progress. I think it will accelerate our ability to understand this disease faster than anything that s come before it. Why are you so passionate about this? Dr. Dunn: We have a chance to improve the human condition what could be better than that. If you have a chance to live and to work and to improve the quality of life of people that you feel are your brothers and sisters in humanity how would you not want a chance to step up and lend a hand. How did you get involved with MS?

8 Dr. Dunn: Immunology is the body s doctor I learned that early on. We did work in molecular immunology at a pioneering time, saw how important that was. As doctors go through training they have a sense, they come across something that just resonates with them, it just seems right. When I would see men and women fighting MS there was something about it that they just felt like my brothers and sisters and to have a chance to help them just felt like a privilege. It didn t even feel like work, it doesn t to this day. 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. If you would like more information, please contact: Jeffrey Dunn, MD Stanford School of Medicine (650) jeffdunn@stanford.edu Sign up for a free weekly on Medical Breakthroughs called First to Know by clicking here.