The Latest in Multiple Sclerosis Research Webcast January 7, 2009 Dennis Bourdette, M.D. Amy Clawson Please remember the opinions expressed on Patient Power are not necessarily the views of Oregon Health & Science University, its staff, our sponsors, partners or Patient Power. Our discussions are not a substitute for seeking medical advice or care from your own doctor. Please have this discussion you re your own doctor, that s how you ll get care that s most appropriate for you. Introduction Hello and welcome to our "Ask the Experts" program produced by Patient Power and sponsored by Oregon Health and Science University. I m Andrew Schorr. We do this every two weeks connecting you with at least one leading OHSU expert and always inspiring patients. I want you to listen for a second. I think you ll be wowed. < Clip from Amy Clawson s Cowboy Up > That s Amy Clawson, and if you live around Oregon you may well know her as a very charismatic contemporary country singer. She s been packing houses for many years now. She s thirty-four years old, but when she was twenty-eight, Amy, there you were on stage in Reno, I believe. What happened? We came in for a sound check and load in, and I got up on stage, did my thing like I always do, and I literally turned to look out and couldn t see out of half of my head. I guess that s the best way to describe it. I kind of looked at one side of the stage and tried to look to the other side, and when I went to move I was kind of walking dizzy. I tried to make a joke out of it and said, Now I know how a drunk feels. They helped me off the stage, took me instantly to the ER, and they suggested I go to an eye specialist. He thought it was my thyroid and sent me to another doctor, and within two weeks they had it diagnosed as MS of course. As multiple sclerosis, and that s our topic, the latest in multiple sclerosis research, today. So Amy, you have carried on as a very popular singer but yet living with MS. So first of all somebody tells you you have this diagnosis. That s like really on a relatively young person dropping a ton of bricks on you, isn t it? Yes. I was about to sign my record label or a record deal and had the world by the tail, as I thought I should have the world by the tail, and God s got a way of giving 1
you a wake-up call, and I think that was definitely mine. Of course I proceeded on for a few more years to do three hundred shows a year just to prove to everybody that I could do it. I realized in the process that that s not how I had to do things, and the only person that could stop me was me, and I kept on living my dreams and just adjusted my skew a little bit. I ve always had my family on the road with me. I ve been very blessed that way. When I got diagnosed I ve always had my family around me. They ve been very positive and very supportive. Of course that s a huge part of it having support of friends and family. I got right away with a good neurologist that got me on proper medication, which helped out so much, but I think just a really good positive attitude is the best thing that you could do when you get any kind of a diagnosis of any magnitude. Yes, I agree. Now let s mention that you received treatment at OHSU, and they have a wonderful center there, the Multiple Sclerosis Center of Oregon and quite a department of neurology that researches MS and has for twenty-five years or so, and someone who s really led the way, the chairman of the department and the director of the center and has been there many years at OHSU is neurologist Dr. Dennis Bourdette, who s your doctor. Dr. Bourdette, I guess we re blessed in one way that you have many medications that are available and approved in MS. We d like to have a cure, and research goes on. We re going to talk about it, but in Amy s case maybe she doesn t try to be quite as crazy in her schedule as one might otherwise, but still she carries on. People can live with MS and in many cases live pretty well, can t they? That s correct. Multiple sclerosis is not a fatal illness, but it certainly can disrupt people s lives and at times can be disabling. I think it is important to emphasize that it s both a treatable condition and also something that people can still live full lives with. I think Amy typifies that. Her emphasis on attitude is very important. I don t have a prescription for that. That s something I can t give to people. They have to find it within themselves, but MS is not a death sentence. It s a condition you have to learn to live with and do things in spite of it. Symptoms of Multiple Sclerosis Doctor, just to help orient people because some who may be listening to this program may be very new to MS. Just help us briefly understand what s gone wrong when someone develops MS. For most people they start off like Amy did where they will develop out of the blue some sort of neurologic problem; loss of vision in one eye, difficulties walking, 2
numbness and tingling from the waist down. They ll get better from that and then will subsequently have other attacks where they develop a recurrence of an old problem or a new neurologic problem. During those spells, what is pretty clear is happening are white blood cells are going from the blood into the brain and the spinal cord and causing damage to the nerve fibers of the electrical system or the nervous system, if you will, and causing the symptoms that the person is experiencing. So early on in MS, and that is in the first few years, there are these episodic attacks of white blood cells going in and causing inflammation, causing damage, and causing symptoms. So it s what you call an autoimmune condition where your body is not behaving, the immune system is not behaving the way it should. That s correct. Amy, now I understand that people with MS can have very vague symptoms that may change over time. So you talked about the vision, and I know you said walking on stage and you weren t steady. What are other things you ve noticed? We traced it back. Of course once you start realizing you go oh wow, this stuff s been happening for a long time. You get paralysis, loss of feeling in lots of places, tingling in the bottom of your feet. I can tilt my head down and just get an electric jolt all the way from the top of my neck all the way out my toes, and you just have to laugh it off. It s just a part of life. Everybody has a cross to bear and that happens to be mine, and with mine came also seizure. Everybody has a different form of MS. Somebody has a different, I don t want to say side effect of the nerve, but everybody does have something different that happens with their nerve damage. Nobody s case is the same, so it s really hard to say who suffers with what, but you can bet they are suffering with something. So it s just the fact that it s invisible to people s eyes. It s a hard disease for people to understand. I think it s what drives a lot of people crazy to have MS is the psychological part of it is that it s hard for them to explain to their loved ones or their friends just exactly what they re going through because they don t really understand it themselves. Amy, but so you re a celebrity, a public personality, and you go on stage. In the course of a year thousands of people and so many people hear your music. Some 3
days you may feel great and some days you may not, so you re public about it now, but what about in your performances? Do you mention it, or does it come up, or do people ask you before or after a show, and what do you say? I talk about it any time. I don t mind in the least bit because the way I look at it is if one person sees me on a good day or a bad day and that inspires them to get up and go, then that s a great thing because I know that there have been hundreds if not thousands of times that I have seen people inspire me to get up and go plenty of times. My father is a cancer survivor a few times over, and I ve seen him get up and go to the farm when he couldn t and he felt unbelievably awful, but the last thing in his mind was staying at home because he had to take care of us. That was the most important thing, and that s just what I m used to seeing. You don t let anything stop you from getting the job at hand done or your dreams done. You just go. Treating MS and Clinical Trials Wow, well said. Now there you were with a chronic condition, and you re giving yourself a shot I think three times a week? Yes. And as many people with MS do the dosage may vary and depending on which medication you re on, but many people are doing or are on what are called the disease-modifying therapies, which fortunately there are several now that are approved, but anyone with MS and a chronic condition keeps their eye on the research front, so we ll talk to your doctor about that for a minute. Dr. Bourdette, so the medicines we have now have made a difference for many people, not everyone, but for many people in hopefully delaying disability, the progression of the disease, and helping people live a fuller life. Where are we now with research, and tell us about what s going on at OHSU that you think may be promising? Let me start off by saying that there are three major problems that we need to conquer in terms of controlling MS. The first is to have effective drugs that will control the inflammation that s causing the damage that I talked about earlier. The second is in people in later stages after they ve had MS for ten/fifteen years, many of them enter a phase called progressive MS where each year they re a little 4
worse than the next, and in that situation there s a progressive death of the electrical wires or the nerve fibers, and we don t really understand that very well, and it s not being driven by white blood cells going from the blood into the brain but by something intrinsic to the brain. So we need to develop therapies to halt that. The third issue is there are a lot of people that have had MS for a number of years and have permanent disability from damage that has occurred. We need to find ways to help promote repair. So there are these three areas of treatment approaches; controlling inflammation, controlling the progressive nerve fiber death, and promoting repair. The current FDA-approved drugs that we have are all aimed at controlling the inflammation, and frankly much of the research that s being done is finding new ways to control inflammation. Our scientists have invented a new antiinflammatory treatment called RTL 1000 that is in the early phases of development. Perhaps I ll tell you just a little bit about that. Sure. RTL 1000 is a, it sounds like an Italian sports car, but it s a bioengineered protein that binds to the disease-causing white blood cells in MS. It actually initially stuns them and then turns them from being disease-causing cells to actually being cells that can promote control of the disease or protective white blood cells. It s a protein that s given by intravenous infusion once a month. It works fabulously in animal models of MS, but of course we re not trying to cure MS in animals, we re trying to cure it in people, so we re in the midst of the first phases of testing it in people with MS. To develop a new drug you go through a series of steps, and we re at the first step where a single injection is given to a small group of patients, and the purpose is to determine what s the highest dose you can give safely, and that study is near completion and should be done by the first part of 2009. Is that what you call a phase-i study? That s exactly what you call it, a phase-i study. There will most likely be a sort of a phase-ib study, which will be again taking the highest dose that was identified in the first step and testing it for safety when given monthly for three-to-six months. Assuming that s shown to be safe the next step will be a phase-ii study where a larger group of patients somewhere on the order of a hundred or so who will either receive the drug or a placebo for six months, and we monitor their response to therapy. 5
We think this RTL 1000, if it proves to be effective, has advantages over current FDA-approved drugs. One is it doesn t require weekly or daily or three-times-aweek injections, but it can be given as an infusion through a vein once a month. Unlike natalizumab, which is a monoclonal antibody that s a very powerful treatment for MS that s currently available, it shouldn t alter the immune system in a way that might set you up for causing serious side effects. One of the big problems with natalizumab and other monoclonal antibodies is that they really dramatically alter the immune system, and in the case of natalizumab there have been some people receiving it that have developed a serious, life-threatening viral infection of the brain, and we don t anticipate RTL 1000 causing problems like that. Wow, it sounds exciting. I was in a clinical trial for leukemia, a phase-ii clinical trial, and the treatment I received, I m a twelve-year leukemia survivor now, that I received actually eight years ago when I started treatment, is what most people get now. So I am a big proponent of our listeners paying attention to the opportunities that may be there in clinical trials. Doctor, if someone is interested in finding out more about this trial or other research at OHSU, is there a phone number to call? Yes there is. They can call 503-494-7241, and they can get that information. Okay, and I ll repeat that for folks if you re listening; 503-494-7241 at the MS Center of Oregon. So Amy, you go to OHSU for care, so you know it s a research place as well as a neurology clinic. When you hear about this that must be exciting I guess that hopefully maybe something better will come along. I was just finishing writing that number down, just a second. I was going to get in that clinical trial. There you go; 503-494-7241. I m volunteering my body to science, yes. Now, yes, the whole reason that I wanted to come up here was that. In fact I had a doctor that, I believe he was a great man, Dr. William Nelson, who wanted me to be at this hospital so badly that his last couple of months that he was in the town I was in he spent his own time making a couple of trips up here to try to get me in, but my insurance would not pay for it. So I took a leap of faith and left my insurance company and went to a disability plan, and they allowed me to come up here. 6
It was all dependent upon me leaving the insurance company solely so that I could come to OHSU because this place is just amazing. Wow, well I think so too, and every time we do one of these programs every two weeks I always see that. Dr. Bourdette, give us a sense of other things. You mentioned about RTL 1000; what are other areas that your researchers are looking into that whether it s in the next couple of years or even ten years down the road that could show promise? Let me first comment on one thing that we re doing that we think is unique. We re actually quite interested in studying complimentary and alternative medicines. So for instance we re hoping to start a trial of investigating the effects of a low-fat diet. It s been an interest for decades in that as being something that is an antiinflammatory diet and might be beneficial in MS. Lots of people with MS actually follow a low-fat diet. Neurologists in general don t advise people to follow any special diet or take any special supplements because there s no evidence to prove that it s beneficial. We ve also led the way in studying some other natural products that we think might be beneficial. We re doing a study right now of ginkgo biloba for cognitive impairment in MS. We ve been developing a natural antioxidant called lipoic acid that we believe is a good antiinflammatory for MS and can be given orally. So we have a whole group of individuals who are studying these more natural approaches and studying them scientifically the same way we would study a drug because that s the only way we re going to be able to determine what works and what doesn t work. Well that brings up a point, and Amy I m sure people in the MS community have said this to you or maybe you too, you know, somebody says well you should try this or take this or you get it at the health food store, etc., and often people are reluctant to tell their M.D. because maybe the M.D. didn t mention it or said he or she didn t know, but you d encourage that kind of open communication with your doctor on everything you re taking whether it s a natural substance or trying a certain diet. That s how we learn and how somebody hopefully can be on track. Amy, are there things you ve tried? I admit totally to telling your doctor everything. I don t care if you went out in the back parking lot and snorted crack before you walked in. You gotta tell your doctor everything, and the point being is because he s the one treating you, and if you had the disease and if you believe in all natural medicine, don t leave it outside the 7
clinic. You ve got to bring it inside the clinic I believe, and a lot of people they have come up to me about all natural treatments, but they won t discuss it with their physicians in the least bit. I came up here and I ve talked to Dr. Bourdette about this specifically for all natural remedies. I wanted to come and try to even pony-back them with my Rebif. I believe that in one conversation just one of the things that we had talked about was he had said that they were talking about green tea extract for MS, and some of the treatments that I was going to try to get into just to see things that I could help with. I mean I have of course memory problems. I have chronic fatigue to the point that I almost have narcolepsy; I fall asleep standing up. You know, there are so many issues that need to be dealt with that you just can t keep pounding drugs down and drugs down and drugs down. You ve got to find other links and a way to help you or you re going to end up having a problem on top of your problem. I believe this hospital helps with that. That s, well, we ve got the head guy with us. Dr. Bourdette, it sounds like your department and your center is very open to that discussion. It sounds like it s an essential discussion. Right, and I think that not all neurologists feel that way. Not all neurologists are open to that possibility that some of these approaches might be beneficial. I think that that s why it s critical that we actually study them and do research on them because that s the only way we re going to determine what works and can convince the neurologic community that some of these approaches are beneficial is actually by doing the research. Bone Marrow Stem Cell Transplantation I ve had the benefit of interviewing some neurologists around the country, and then there was one immunologist I interviewed where, and I guess it s come up in a couple of places, and I d be interested to know your thoughts about it whether in extreme cases there s a role for stem cell transplant or anything known about it that someone could make a decision on at this point? I think the stem cell transplants you re talking about are the bone marrow stem cell transplants where one harvests these stem cells from the bone marrow and then gives high-dose chemotherapy and then reconstitutes it by giving the person back their own stem cells. That s been studied for a number of years now. I think the problem is that while there have been advances in making that approach safer, there s still a risk of people dying from that procedure. If you re having the stem cell transplant because 8
you re being treated for leukemia or lymphoma that s one thing. In the case of MS it s not a fatal illness so it s hard to justify putting patients at risk of, even if it s one chance out of twenty of actually having a life-threatening complication. There might be the occasional person with a very, very active case of MS that might benefit from that. So far I ve not seen that patient. We are usually able even in people with very active inflammation to come up with therapies that aren t quite as aggressive that provides benefit. Amy, for you now, so you alluded to the fact that you ve cut back on your schedule some. You sort of faced your situation but still continuing to entertain and motivate people. What s your hope for the future? I ve been, by the grace of God, been able to do what I do for twenty-two years, and I ve never had to do anything but entertain, and I just pray that that s all I ever have to do. I ve been lucky so far, and MS hasn t stopped that. There have been a couple of shows that have stopped because of seizures. Really kind of that was a finale. I really couldn t top that one, so the shows were over. Other than that I think the show goes on, and until I absolutely, I m going to say I ll wheel out on the stage, I don t mind that, but until I absolutely can t sing anymore or my speech is just completely gone I ll be singing. My hopes and dreams are just that they can find something that can help people and people get educated about it, but until then just to keep doing what I m doing. Doctor, it s really a partnership between people like Amy who are living with MS and a research center such as yours not just to provide good daily care but also to try to get answers long term, isn t it? I like the term partnership. I think that first of all in terms of research we can get ideas from people reporting back things that they found that have helped them, but even more importantly we can t do research on MS without people volunteering to participate in trials. They re the real heroes of any advances we make in developing theories for MS, the people who volunteered to participate in trials. You re familiar with that. It s a real active leap of faith. It s an altruistic act to go into a trial where you don t know for sure whether there might be some unexpected side effects. Some trials you might be getting a placebo. So they re the real hereos, and that s part of the partnership. I think that from my point of view as a physician, I see working with people with MS as a partnership. It s not me. I m not the boss of telling the patient what to do, but we have to work together to come up with treatments that work for the person, and I need to be respectful of what they want to do. My whole goal is to help people live as full a life as possible. So that means I need to view myself as their 9
trusted confidant and advisor about their health, but ultimately the decisions about what a person s going to do they need to make with my assistance. So I think that the doctor/patient relationship, that definitely has to be a partnership. Dr. Bourdette, I know you ve been at this a long time, at least a quarter of a century, and people must ask you all the time, and I know that MS is very variable among people and even over the course of time with one person, but are you hopeful that we ll do better? We re already doing better. The first ten years of my practice we didn t have any of these FDA approved drugs, and at any given time I always had one patient in the hospital with a really bad attack of MS that we were treating; now maybe I ll have two a year. So the currently available drugs, particularly when we start them within the first few years of onset, are definitely helping to control the MS. They re not cures. They don t work in everybody. They have their side effects, but we ve already seen in my career substantial improvements in our ability to treat MS. There is so much outstanding and exciting research going on not only at OHSU but at MS centers all over the world that I believe what we re going to see is continued improvement in our ability to treat MS. Dr. Dennis Bourdette, we re going to give the last word to your patient, Amy, but I want to congratulate you on all the work you and your team does at the MS Center of Oregon and in your neurology department at OHSU and you personally for your decades of dedication to patients. Amy, so we talked about you keeping on inspiring people, but is there a comment you d want to make to Dr. Bourdette, after all he runs a big center, on how you may be representing how patients feel about the work they do? Oh wow, you know, I don t know that one comment covers it, but I was very, very thankful. I remember jumping up from the computer when I got an e-mail from Dr. Bourdette asking if I d like to come see him for an appointment, and I was so excited; I was elated, and I had just given up on doctors period. So to see him and then to meet him, and I so do not mean any disrespect on any neurologists that are listening to this, but neurologists are generally freaky people, and he s not. I mean, he s just not. He s a very, very genuinely nice man. It s just that I think they re just really so smart they just can t talk to most people, and he s not that way. He generally cares about you and really wants to find out not by reading other doctors notes but by listening to you and finding out what s going on with you so that he can make things the best for you. He doesn t lump you into his other MS patients. He doesn t generalize everything, and they re all about making your life better, the quality of your life better and your family s quality of life better, and I believe that 10
when he goes to bed at night, when he lays his head on his pillow, he can honestly lay it down and go to sleep with a clear conscience because he knows that he s given everything in his heart that day to his patients here at the hospital. I mean, if you met him in person you would know he s just a wonderful man. I feel very fortunate that God put our paths to cross. Wow. Well you know what he s going to say back home tonight is he s going to say, Amy Clawson said I m not one of those freaky people. <Laughing> There you go Amy. Dr. Bourdette, congratulations. <Laughing> There you go. Well thank you so much for being with us. Amy we love listening to your music, and I know for the people who are blessed in seeing you perform in person and knowing what s going on behind the scenes that really it s a great inspiration. Thanks for having me. God bless you on your cancer too. Thank you. Well that s why we re all out there trying to help others, all three of us. Thank you so much for being with us. This is what we do on our "Ask the Experts" program, and I m so delighted to be associated as we are with meeting the inspiring patients and experts from Oregon Health and Science University. So if you, our listeners, can join us every two weeks we do a program like this. The topics vary, but they re always very memorable, and you can always send us an e- mail of course to experts@ohsu.edu. I m Andrew Schorr. Remember, knowledge can be the best medicine of all. Please remember the opinions expressed on Patient Power are not necessarily the views of Oregon Health & Science University, its staff, our sponsors, partners or Patient Power. Our discussions are not a substitute for seeking medical advice or care from your own doctor. Please have this discussion you re your own doctor, that s how you ll get care that s most appropriate for you. 11