>> rose: tonight's a special edition of the charlie rose brain series, year two. in our 9th episode we consider multiple sclerosis. episode 9 of the charlie rose brain series 2, underwritten by the siemens foundation. >> multiple sclerosis is an autoimmune disease. so the immune system developed in order to protect us against foreign invaders like viruses and bacteria. and on occasion it errs and recognizes a protein in the body and becomes the target of an i pun attack. it's been obvious to pain people all along that the variety of organs in the body that are susceptible to this kind of attack. for example we have known that type 1 diabetes is an autoimmune disease that hits cells in the pancreas that release insulin or crohn's disease is an autoimmune disease that affects the bowel testimony has been less obvious although it is perfectly clear that autoimmune diseases also

affect the brain even though the brain has this protective barrier called the blood brain barrier, auto immune disease can penetrate that and attack it. and this is where we see multiple sclerosis. >> rose: the charlie rose brain series is about the most exciting scientific experience of our time. >> understanding the brain. this series is paid possible by a grant from the siemens foundation. their mission is to advance the frontiers of research in the basic sciences and mathematics. >> funding for charlie rose was provided by the following:

captioning sponsored by rose communications from our studios in new york city, this is charlie rose. >> rose: tonight we continue our exploration into our magnificent brain with a look at multiple sclerosis it is an autoimmune disease that affects the central nervous system it is caused by damage to the myelin

sheath protective covering that surrounds nerve cells. when damaged nerve signals slow done or stop. this can occur along any area of the brain, optic nerve and spinal chord. ms is most commonly diagnosed between ages 20 and 40 but could be seen at any age it affects twice as many women as men. one of them joined me this evening, andrea kirkpatrick is president and founder of the nonprofit cool kids learn. in 2001 she was diagnosed with ms. also here a remarkable group of scientist, stephen hauser of the nearology department of university of san francisco, amit bar-or of the unit of mcgrill. alfred sandock from harvard medical school and once again my friend and cohost dr. eric kandel. he is as you foe by now a nobel laureate, professor at columbia university and a howard hughes medical investigator. welcome to one and all. i begin with you as always, eric. tell me what we will discover this evening. >> in the last program we considered huntington's disease and parkinson's

disease. these are protein-folding disorders that cause degeneration of the nervous system. today we're going to consider a deagain rattive disease, multiple ser sclero that has a very different cause. it is an autoimmune disease. so the immune system developed in order to protect us against foreign invaders like viruses and bacteria. and an occasion it errs and recognizes protein in the body and becomes the target of an immune attack. it's been obvious to many people all along that the variety of organs in the body that are susceptible to this kind of attack. for example, we've known that type 1 diabetes is an autoimmune disease that hits cells in the pancreas, that release insulin or crohn's disease is an autoimmune disease that affects the bowel it has been less obvious although it's perfectly clear that autoimmune diseases also affect the brain even though the brain has this protective barrier called the blood-brain barrier,

autoimmune disease can penetrate that and attack it. and this is where we see a multiple sclerosis. what causes this immune attack and multiple sclerosis is not completely clear. there are a number of environmental and genetic factors that are known to contribute, so for example certain kind of viral infections make you more susceptible to multiple sclerosis. and also if you have two identical twins and one of them has multiple sclerosis, the chances are 30% that the other one will have it. so there clearly is a genetic contribution to this. and if you have additional family members, the incidence will ri. the target of the disease is the myelin sheath. so many axe ons in the brain are-- axeons in the brain are covered with this fatty sheath that is designed to enhance conduction along the axeon. there are some unmyelin ated axeons but there are lots in the nervous system and if you attack that in an autoimmune disorder like multiple sclerosis, you can

slow and ultimately stop conduction in those axeons. because myelin axeons are throughout the brain, you can affect many different parts of the brain as a result of the autoimmune disease. if you hit the optic nerve you can have transient blindness. if you hit the spinal chord or the brain, you can have sense ory disturbances, tremors, you can have weaknesses in an arm or a leg. these episodes vary in duration. they can last for days. they can last for weeks and they can last for months. but you can have periods in between them in which you are relatively free of symptoms. in is more common in women than in men. but women tolerate the disease better than men in many cases. the incidence is about one in a thousand. and for reasons one doesn't quite understand, there is an increase in incidence both in the united states and in other parts of the world over the last 15

years. but that downer aside, there is a lot of optimism in the field n part because of these four people here. we have with us andrea who is really the structure of the whole program. she sort of designed the program around herself. she brought with herr support team. >> rose: right. >> and these three gentlemen are here in order to sort of fill out what we need to foe about her disorder, multiple sclerosis and her disease in specific. so steve hauser is her physician. he's a leading investigator of multiple sclerosis and he brought with him amit and al who are his colleagues even though they work at different institutions. amit studies what goes wrong in multiple sclerosis, the mechanism pathogenesis. and al is developing new wonder drugs that really not only stop the disease but are capable of reversing it.

so there is an optimism in the field that this is perhaps the single most treatable disorder of neurological diseases. and we'll see in andrea's case that these people not only will bring independent, four independent perspectives of multiple sclerosises but they have collaborated together in order to improve her clinical situation. and actually reversed some of her symptoms. and obviously what is beneficial for her is going to be beneficial for everyone. so this is really providing a completely new approach to the disorder. and so she has brought with herr team, hopefully a dream team but we'll see as we go along. >> rose: thank you very much. stephen hauser, let me begin with you. drill down a bit in terms of understanding multiple sclerosis. >> sure. ms is without question one of the great triumphs but also one of the great mysteries still in medicine. why has it increased in

frequency so much over the past 100 years and why has this increase been almost entirely in women? we know for certain that ms is an inflammation, that myelin is targeted by our immune systems. and that this targeting of myelin causing inflammation and scarring occurs in a repit-- repetitive way over years. very important, the scarring not only disrupts nerve transmission as eric mentioned, but it leads to a late degeneration of nerve cells. so it becomes a nerve deagain rattive disease in its late phases. and untreated most people with ms develop disability, were unable to work or walk or interact deeply with their-- with society. but that all has changed as we will hear today. the symptoms of ms are symptoms due to the disruption of important pathways. numbness, weakness, double

vision, loss of vision in one eye, incoordination, bowel and bladder difficult, cog knittive slowing. these are all symptoms of multiple sclerosis. mr. s is the most common cause of symptoms of this nature that arise in early to mid adulthood. the mri scan has really revolutionized our thinking and understanding about ms. we can actually visualize in real life a person with multiple sclerosis. the myelin is in the central parts of the brain. and this is a picture just above the ears, horizontal photo of the brain. and normal myelin is black. and the scars of multiple sclerosis and the inflammation are in white. and here over the course of a few years one can see in the left upper corner the inflammation begin and then scar damage and regress and other areas begin and

regress in other parts of the brain. we've learned from the mri that most of the activity in ms occurs below the surface. people don't have symptoms. they may feel unwell. fat agency is an important symptom but over the course of time this can lead to a progressive deagain rattive process. and the great news is that if we can stop the inflammation early we can protect people against this late degeneration. >> can you stop it in you can't detect it early enough? >> we, one needs to detect it in order to stop it. >> i think one of the wonderful things that has come along is the ability to visualize these lesions in the brain. this is only with the development of magnetic resonance centre imaging that one has been able to do this. >> how long before, in other words, between the onset and there is detection, what is an all time so it spreads rapidly. >> it depends upon the

individual person. only about one in seven of those bright spots that you can see on the scan causes symptoms. so for some people the symptoms are evident at the beginning. in others it takes two or three years for symptoms to appear. >> okay. take us now to this experience that you have had and a sense of what it was like, how you discovered it, where are you today? >> my ms was first diagnosed in 2001. before that i led a very active life mainly because of work. i was a management consultant. i worked for years in new york and san francisco and miami. i served clients across the world. i was flying a lot, working late hours. doing, i guess what people do in that part of their career where they are building. and then suddenly i think i was at a training program, actually, i noticed that i couldn't see very well just out of one of my eyes, my left eye.

and i kind of said oh it's just stress. i'm working too hard or i'm getting older, i need to go see a doctor about eyeglasses. but somebody i was on the program with said no, that's really serious, you shouldn't detect such a difference. go check it out. so i did go and saw a couple op thom all gist but nobody could tell me what it was but they couldn't figure out how to fit me for a pair of glasses that would actually work. then i started noticing that i was feeling tingling in my fingers like when you have pins and needles when your foot falls asleep but 2 would never go away. and i mentioned it to my mother in passing one day. and of course as a mother she kind of was very concerned about thisment and she went on-line and she checked things out and one day she called me and said i think i know what it is. i think you have ms. i think that is what it. and i thought oh, you're being dramatic, you are a's a mom. but she convinced me to go have an mri. and as soon as they did it they could see it crystal clear. there was to doubt that that is what it was.

so that is when i discovered that i had the disease. and went in search of the best person to help me with it. >> rose: so what has happened since then. >> my symptoms have been mainly tingling, numbness. so i can wake up and i will feel that my arm is numb or my midsection is numb. sometimes i would feel that, for example, one of my feet didn't want to move quite as well as the other one. it never got to the point where i would stumble or fall. i didn't have any pain. but i just was not very coordinated. and those symptoms kind of came and went over the years. >> rose: tell us pore about the mechanism behind this. >> well, the first step for understanding ms, it's worth taking a look at this first image which depicts the basic building block of the central nervous system this is the neuron and on the left-hand side you see the

cell body of the neuron. and then extending from the neuron is the axon. it is what carries the information, the impulse that is generated in the neuron it travels down the axe on and then can communicate with additional cells of the never vows system such as neurons through a little space that's called a synapse or other neurons and axons may connect to their muscles. these neuroons an ca, xons carry information in and out of the central nervous system if they are injured any of the symptoms steve mention kd emerge. the speed of transmission in this neuron and axon can be up to about 10 meters per second which may sound relatively fast. but in fact while that might work well for small animal like a fly or a worm, once the animal gets big enough, that speed of transmission is actually rather slow. so what evolution has cleverly been able to do is to wrap these axeons with an insurance lating material that eric had mentioned earlier called myelin. and this fatty material is

wrapped around the axon such that there are tiny spaces to you between the myelin ated sections, the nodes of romvia and now the impulse doesn't have to travel throughout the length of the axon but it bounces from one node to another. this is called saltatory propagation. and the speeds now can be up to 150 meters per second so that the efficiency of the transmission in the central nervous system for many pathways which are myelin ated depend on this insulation to be able to mount that speed of conduction there are also nonmyelinated fibers in the nervous system and these serve different purposes. now as steve had mentioned, our view of ms is that there is an activation of immune cells inappropriately in the periphery, that they then traffic across this blood brain barrier that eric had spoken of. and then injury the myelin and sometimes the underlying axon. disruption of the myelin will result in slowed conduction, symptoms such as slowness of movement or

weaknessment but transsection or break in the continuity of the axon itself may result in failure of conduction entirely. >> rose: eric, what i don't understand and want to make sure i understand what is it that causes autoimmune system to be triggered so that it begins to attack something that is not hostile but is, in fact, necessary? >> one doesn't really know. >> rose: that is the big question. >> we don't really know this in detail. we know genetic factors can contribute. an certain kind of viral infections predispose you to it. but somehow the immune system recognizes a normal molecule n this case myelin protein as being an outside agent, that attacks it if it was a foreign substance. >> so connect this to other autoimmune diseases for us. >> so there are many connections, and in fact many autoimmune diseases like ms are increasing in frequency. and some have wondered why as our society changes our

immune system begins to react against our own tissues instead of against abnormallal tissues such as cancer or invading infectious organisms. and we don't have the answer. we assume that the trigger is in the environment. and it's some infectious agent, perhaps an infectious agent against which we're exposed at a later age than we would have earlier. >> but what would be the suspects. >> in multiple sclerosis probably the best suspect that we have is the epstein-barr virus which is a learn es virus that 80% of the world's population is infected with. but in western society, prone to ms, we are this infected at a later age and the consequence of that infection is often a problem called infectious monday owe knew clio sis, the kissing disease that happens not uncommonly in adolescence. and people who are exposed to epstein-barr virus at a

later age in life are clearly at higher risk for multiple sclerosis. we also think that a deficiency in vitamin d perhaps resulting from less sun exposure may be a culprit that activates the immune system making some of us pore susceptible. >> in fact there is a geographic distribution, isn't there. >> yes, there is, yes, there is. >> genetics has always dramatically changed our understanding of what makes some people susceptible to autoimmune diseases. we have 23,000 genes in each of our cells. they come in different sequences or flavors. and about 60 of those flavors, 60 genes are inherited by people who are at risk for multiple sclerosis. and interestingly, these genes are overwhelmingly genes of the immune system.

and for other autoimmune diseases some of the same genes play a role in determining at least part of the risk. and in people who are susceptible to multiple sclerosis in their families, there is also often a susceptibility to other autoimmune problems in the skin, psoriasis, in the bowels, colitis, thyroid, type 1 diabetes, when the inflammation hits the pancreas, et cetera. >> rose: so if you found the solution to one it might lead you to an understanding of the other autoimmune diseases. >> absolutely. and knowledge about what helps another disease with the genetic understanding can lead us to valuable therapies that might be useful for ms. >> when you look at the genes that are involved in autoimmune diseases and other neurological diseases, that ms is more with other autoimmune diseases is -- >> so the remarkable story about the genetic

understanding of multiple sclerosis is that sus september ability clusters with the other autoimmune diseases and not at all with the diseases that we've spoken about on earlier segments of this show. the deagain rattive diseases are all the way in a different category. >> that bring me to you, the question is how does this biological understanding help us think about some kind of intervention. >> yes. well first to say that we have known about ms for about 150 years. charcot described it way back then, it's only in the last 20 or so years that we actually have treatments that are disease-modifying. in fact, when i was training in neurology at mass general with steve hauser, we had very little we could offer our patients. but at the beginning about 20 years ago, we found a beta interferons and copaxon seemed to work in ms by decreasing the inflammation

you can see in the brain. and we can actually see that in the mri scans. and they seem to work by modulating the immune system in some way. and actually there are lots of different theories about how that happens. it's not entirely clear but it is-- what is clear is that the immune system is being affected by these therapies. the problem with those therapies was that they were relatively modest in efficacy. there were inconvenient because they were injectables. some were every day injections. others were every other day or once a week. so that left a high unmet need. and using the understanding of the biology of ms, many people went after better drugs. and about six or so years ago tysabri was the next drug to be approved. it works in a very interesting way. we learned over the years that immune cells when they invade the brain they have to first attach to the blood vessel wall.

using very specific molecules. so-called adhesion molecules. it's like val crow-- velcro. if that doesn't occur, these cells can't get into the brain. so knowing that the molecular understanding of that velcro interaction, if you will, we made an ants body called tysabri that blocks the interaction between two of these key molecules. and it's very effective when you treat people with this drug intravenously it prevents these white blood cells that want to get in and attack the brain t prevents them from getting into the brain and they stay if the bloodstream. so that is how tysabri is thought to, wochlt and more recently we've had new additions to the ms therapeutic landscape. we have the first oral medication approved called gilenia. this drug is interesting in that it seems to block the egress of immune cells out of lymph nodes. so obviously they can't get into the brain. but they basically are

locked into the lymph nodes preventing them from escaping there and to do damage. and i think gilania will be the first of several orals that will become available. so today we have multiple treatment option force ms patients. >> tysabr circumstances intravenous. >> yes. so here is what is exciting about it. the mystery of it all for what you do is-- if this almost element causes this to happen and this has to travel to there, if we can prevent it from traveling to there, then we can have a huge ben anything effect. >> yes. >> that's the great puzzle solve that draws people to scientific and mathematical research. >> what is so nice about this is that these people interact, they spoke to each other about this illness in order to work out the optimal treatment. >> oh, continue. so you are optimistic now about not only the kinds of things you can do to interrupt the pathways but also genetic understanding that might lead to some kind of --

>> well, i think these genes are shining a bright light on the pathways, the biological pathways that lead to ms. and those of us without want to develop drugs, we're looking within those pathways for targets. you know, are there drugable targets that we can go after. either with anti-bodies or small molecules or some other methods. and so people, it's been great to have this list of 60, hopefully there will be more. because there is still an unmet need in ms and we need to tackle it with -- >> what is so nice about drugs that -- keep limb foe cites from leaving the lymph nodes but they might work in other autoimmune diseases well. >> and the limb foe sites are happy in the limb 6-- lymph node, they are work and protecting us from infection. tysabri is a great story because the million cool that's targeted was initially discovered in a laboratory

as being critical for cells getting across the blood-brain barrier. and then the gene that is targeted by tysabri, its product, which is a protein is one of the 60 genes that was found through genetics. so there is a beautiful convergence that makes an impact at the bedside. >> rose: so we have begun to understand what the beguns are, the mechanisms of it. and now opening the door to treatment. give us your own personal experience here. >> i tried several treatments as they became available. so initially i was on copaxon and then went to an interferon and for me as dr. hauser said, my scans always looked worse than my symptoms presented. but there was always in the back of my mind the thought that at any day i could catch up and look like i should look. and so you know, so we tried several things. and as you said, injectable,

not very pleasant. but i think every time we went and checked my mries there wasn't really the arresting of the disease that we had hoped to see. so one day when i went to see dr. hauser he said okay, now there's a new treatment. it's tysabri and we've had tremendous success with it. and i think you should try it. and so we did. and for me, it has certainly made a difference. so now my mries match my physical condition. and i just do feel overall better, just well in a way that i didn't feel before. >>rose: so what is your hope and dream. >> my hope is that you know, i hear us talk about remyelination. so you know, i know that my disease is arrested or at least it seems to be. i would love it to be-- to be cured. it's not. it's still just controlled.

and i know that that's the pipe dream of everybody. but that would be my dream. >> rose: that is the pipe dream s it not. >> yeah. >> rose: now is she just one lucky person, a because when she discovered that she had this remarkable group of people, and is what happened to her what happens to most people who are diagnosed with ms? in other words, is she one special person because she has access to and is under the care of three great doctors? >> ms can vary from being a trivial to a devastating problem. and every person is a little bit different. but in the population as a whole, the prognosis for multiple sclerosis is far better than it was ten years ago. and this is in large part due to what is now eight wonderful medicines for ms with more coming in the next

couple of years. >> rose: would you add anything to the evolution she has described in terms of her treatment? >> no, i think that andrea described it exactly. andrea had about five attacks in the first three years of disease. had very minor attacks, just little episodes of numbness. but the mri scan that showed far more disease percolating under the surface than we could detect by just speaking with each other, and that we could see on an examination. i can show you a typical example of andrea's mri. >> this is her mri scan. >> we can see it. >> and on the right side of the screen up towards the front you can see that bright white circle. that is the area of inflammation and all of the other lighter white material is the scarring in the white matter. and this was a typical scan

prior to us beginning tysabri. since beginning tysabri, the next slide shows the resolution of that huge area of inflammaon into a very small scar that you can see. and a complete stabilization, with the scars still there, but no new disease activity. so this is quite remarkable. and as al had mentioned, we are using the mri scan much as an internist will use a blood glucose to follow diabetes. this is how we are following multiple sclerosis. >> you helped develop this drug, did you not? you developed it when you were at biogen. >> still there. >> so but it is readily available to people. >> yes. >> this is a drug that is now in wide use. >> it's approved in the

united states. there is a restrict-- there is a registry, a strict method by which you can get the drug. it's called the touch registry. and the reason for that is that there's a side effect that is uncommon but can be quite harmful. >> rose: which is. >> it's called pml which stands for progressive multifocal lukeo encephalopathy. >> rose: which is. >> a viral infection of the grain. and so you know, as we were saying the immune system was there to, you know, prevent viral infections or stave them off. perhaps by blocking the entry of immune cells into the brain, these viruses can now live better in the brain. interestingly enough we don't see a whole lot of other infections. we just see this one. so we are still missing the biology of when we get this

onement but when we first approved tysabri, actually it was approved twice in the united states. the first time it was approved was three months after it was introduced, that we found out about two cases of pml. in fact one case was in san francisco and steve hauser's department. and we stopped all dosing. we pulled the drug off the market because we felt we had to understand the safety. and we had three goals, basically, to understand what is the risk, who is at risk and how can we mitigate the risk. and we spent a lot of time working on those three questions. we've come a long way to understanding that. we now know what the risk is. we know there are three risk factors. one the the duration of treatment. the other one is if you've used prior immunosuppressive drugs, you increase the risk. and finally we just developed a new test that was just approved by the fda this year, an ant i body

test to see whether or not a person is carrying or has been exposed to the virus that causes pml. so the thinking there is that if you haven't been exposed to the virus that causes pml your risk of getting pml must be very, very low. and our data would suggest that. and so people, so the way i look at it is we provided some answers and some tools by which doctors and their patients can figure out what's the right drug for them. as you notice in andrea's history, it's not always easy to figure out what is the right drug. some patient does pretty well on copaxon or interferon but many don't. many need something else. and so how do we choose these drugs. and steve is a very, is an excellent neurologist. he made the right choice here. but we would like to give doctors more tools to help them decide was's the right drug for them. >> rose: so what do you tell

your patients now? >> well, that is the key question. our patients are determined the treatment that they will get. but they are heavily influenced by the manner in which we present this to them. in medical school we're all taught to first of all do no harm. but if we take that to an excess level of conservatism, we will not help our patients with treatments that on average produce great benefits. so this is the conundrum and this is where the art of medicine supersedes the science of medicine. andrea, when we discussed this and andrea knew that her risk of this virus infection was about one in a thousand each year, how did you calculate the cost and benefit? >> i think for me it was a

matter of as i said, i was fine but i always knew in the back of my mind that i might not be fine tomorrow. that the quality of my life might become considerably worse. and you am given me enough information that led me to believe that the benefits of this drug would far outweigh the increased risk. and i thought to myself what will i feel, will i feel worse if i do not switch treatment? and something happens to me that i didn't take the chance to do it? or will i feel worse that i did take the chance to keep my quality of life as it is. and i happen to be a person who fell into that very small percentage. and i thought i will feel worse if i didn't try to do all that i could do to maintain my quality of life. >> i think this discussion is to profound because i think it points out which really needs to be pointed

out in a set of programs like you and i are doing, that medicine is not physics. there are uncertainties involved, and many decisions that are made in medicine. and the way you resolve that is with very honest and difficult discussions between the patient and the physician. and this is really a example of how this should be carried out. >> it certainly is. and it is such an individual decision. >> absolutely. >> based on how an individual assesses their own -- >> yes, and it also is a reflection really of modern medicine. we were discussing this before. when we were-- offices another century ago, we were encouraged by seniors not to be frank with our patients. not to inform them when they had cancer or not to inform them they had multiple sclerosis in the early stages. we would tell the family. we would not tell the patient because we thought this was damaging to the patient. we didn't realize that not being truthful to the patient is probably the most

damaging thing you can do. and the integrity, basic trust is the fundamental basis on which a therapist patient relationship can be based. >> rose: so it has changed. >> yes. >> rose: some have said that the greatest advance in the last decade in molecular medicine has come in aids and multiple sclero schrerx would you share that judgement? >> i think that's the case. and i think that the fiel is imbued with a sense of great hope that the glass which is now half full can become completely full if we can martial the young talent and the resources necessary to make this happen. that better treatments are certainly on the horizon. that cures, the word you used can be for the first time conceived of. that repair is now possible

and that even prevention, repair of damage, and even prevention of ms before it begins in people as inherent ris something something that is now possible. >> rose: are you today better than you were at an earlier period in your relationship with ms? >> yes. absolutely. i have no tactical, tacti symptoms. no tingling, no numbness, no vision-- yeah, no, it's completely arrested. >> rose: how do you fine a diagnostic tool that will allow you to see it before it expresses itself in symptoms? >> difficult. there's a condition that occurs not infrequently where people have a concussion, perhaps from an auto accident or have migraine and have an mri and they are found to have ms

that was inapparent to them. but that gives you an idea. routine brain scans might not be a bad idea. this is what charlie is getting at. that you know you have ekgs even though you don't have heart disease t is just done routinely. this is not a dangerous procedure. >> there is no downside for routine brain scan. >> so this is what i-- a routine brain scan would have discovered this. >> a routine scan would have discovered this. >> then why don't we send everybody out for a routine brain scan tomorrow. >> we are now in a position, we're nw in a position where people directly are accessing deep personal information about their health. >> right. >> body scans. >> right. >> genetic profiles, et cetera. so the cat is out of the bag in many respects in this regard. and our challenge will be how to have an information data bates that is as useful as the overly complex data

that people are receiving. >> and the database you mean not only your own profile but also how it matches up with a whole range of other things that are in the database. >> exactly. what does it mean. so if one has scarring but that scarring is inconsequential and a thousand people began tysabri because of that inapparent scarring, we would be hurting one person without developed pml. >> he's paging a very good point. so you see andrea's scan. and you see that there is this inflammation. and you realize this is related to multiple sclerosis. but if you didn't know her history, and you just saw that, you wouldn't know which of several causes including innocuous ones give rise to that so you need additional information, like family history, genetics, et cetera, et cetera. that is issue number one. issue number two w time we will have additional markers that will say this is multiple sclerosis. this is aldz alz disease

this is front to temperal dementia. so the scan together with additional markers can really pinpoint which specific diseases we're looking at. >> so what is going on within the drug community of the private sector. >> so we're all heavily invested in ms. we think that we're very excited about the progress we've made so far. >> have there been the kind of profit generating drugs, you know like something like lipitor on a grand scale becomes, that enable you to go forward full speed ahead? >> yes, yes. >> they are extremely successful company. >> we are, you know, the reimbursements are quite good. and a big chunk of the profit goes into research and development. one of the things we're very excited about and steve mentioned this, is this idea of repair. as we saw there are a lot of white spots. >> rose: which she has experienced. >> exactly.

but there's still a lot of white spots left in her brain. and those are scars. and when you look under a microscope at some of these regions, you see axons that have not been remyelinated. there is actually an attempt by the body to remyelinate particularly in younger patients. do you see some evidence of remyelination but it's usually very incomplete. and when you look in these-- . >> rose: that is an amazing phenomenon in itself. >> it is. and you look further and you say well y don't you get more remyelination. >> rose: and how dow help it. >> and how do you help it. and when you look in those lesions you actually see that the cells that could do the remyelination are there. >> i want to mention the name of the cell called the oligodendra so we mentioned the myelin and showed how it wraps around axons. the myelin comes from oligodendra sites that are cells that look a little

like an octopus in the picture because it has lots of armsment but these processes go out and actually associate with the nerve fibers. and ultimately they start to wrap membranes around the axons. >> so these are not nerve cells. these are called glio cells. >> that's right. and so a lot of work is going into studying these cells. next slide shows what happens when you have demyelination. obviously the myelin is stripped off here. what we see is that if we don't have remyelination, frequently the axons will slowly die away. the presence of myelin is actually protected for the survival of nerve nerve fibers, so obviously putting myelin back on would help with the nerve con suction-- nerve conduction all the issues it that we talked about but actually may protect the nerve fibers from further damage down the line. and so we would like to put myelin back on as shown there by remyelinating which would we hope produce functional recovery.

now the mystery is why doesn't it happen more fully. >> yeah. >> and it turns out that there are proteins that are expressed by oligodendr sites that seem to inhibit myelin formation. you can take these cells out and put them in a petrie dish. and on the left side what you see are the cells that have a protein called lingo on the surface. that is preventing them from putting out those processes that can lead to myelin. on the right what we've done is we have inhibitied the lingo by using an anti-body to lingo so we have anti-lingo blocking the action of lingo which should release oligodendra sites from the inhi bibt that lingo provide swons the inhi base of modernation that he is-- . >> rose: let me put together, mainly it is this idea we talked about the remarkable achievement in terms of aids

and in terms of ms. we have also talked about some of the difficulties we look at and some have said to me it remains one of the great mysteries, multiple sqler sclero, in fully understanding it. some of the questions we've raised that we don't understand yet there is as i read a sense that a complete cure is possible and can you say a complete cure is in sight. >> those are the questions that people have foremost on their mind. the question of a cure is an interesting one because when we in the clinic discuss this with patients different people actually will define it differently. there are individuals who are effected relatively mildly by ms and for them to stop any further injury would be sufficient. others will in fact require that there be not only no new progression but everything that they are experiencing that they're not happy with go away. which gets back to this very

important concept of repair so with respect to the unmet needs and the time that it will take to get there i think that on the near horizon we are increasingly able and will be pretty good at stopping further damage. this has been accomplished quite well and is becoming even better accomplished in the context of the relapses that patients experience over time. one of the great mysteries that people refer to is that there is this problem of progressive disease that appears to take on a course of its own even independent of these new relapses. and many of the treatments that have been fairly effective at stopping relapses do not appear to sufficiently change the trajectory of this progression. so in terms of an unknown what is the biology that underlies that, the degeneration that tif was referring to before and how likely might might we target those processes that seem to be playing out now within the central nervous system relatively independently of waves of inflammation coming from the outside. there is a lot of discussion about inflammation residing

within the cns itself and preventing the repair that otherwise could be enabled or promoted with a type of medication such as the anti-lingo. and furthermore in terms of mysteries that we have, if you go all the way back to the beginning of the ms spectrum, we don't really know what the initial triggers are. and we don't really know what the initial targets are. >> rose: we don't even know where the triggers come from, do we. >> that's correct. it turns out that when an adult develops the first attack that turns out to have been the first clinical attack of ms they probably biologically had onset of their ms many years if not decades prior. and there is some fascinating migration studies over the years. we refer to ms to the being randomly distributed around the globe there are areas where there is more ms and less ms. if you ask the interesting question what happens if an individual goes from an area of high risk to an area of low risk, will they take with them the high risk from the place they came from or acquire the lower risk of the place that they went to.

>> he a very good question. >> do you know what the answer is to that. depends how old you were when you migrated. and that suggests if you leave after a certain age you carry with you the risk from the country you came from. if you leave earlier, you will acquire the risk of the place you go to. and that suggests that the actual biological onset of ms occurs probably many years if not decades prior to the first clinical symptoms. >> rose: so what is the age there, where is it you do carries it, you don't carry it. >> probably around puberty, maybe even prepu betterally and some think even earlier it turns out that ms can occur in children. it's about 100 times less common. but there are children even ages of 2, 3 who can have a first attack of what later turns out to be multiple sclerosis. and you can imagine the experience as a child, to the family, to the caregivers and how difficult that is. there is a great unmet need in understanding why that

emerges in some people so early and also a great opportunity to try to understand biologically what might be happening as close to the beginning as possible. on the average, when ms first emerges in children, they will be closer biologically to the actual onset and some of the findings from these types of cohorts that are being followed in different countries are beginning to give us clues that the targets of the initial attack may not be the traditional ones that we thought of. and they perhaps may not be first the myelin itself but maybe those nodes of ronvier where there are particular connections between the oligodendr site myelin as it dives down and connects to the axon. and you can imagine how targeting that apparatus can result in the unraveling we see in the context of ms. >> i assume you have asked this question before. and so i ask you what answers have you found. why more women than men? >> that's one of the great unknown questions. a hundred years ago ms was

as common in women as in men. in the 1950s it was 2 to 1, by the 70s, two and a half to one and now new cases are more than three to one, women to men. what has change-- what has changed. we think that smoking is different in women who have ms than women without don't. they are more likely to smoke. but that is a confounder which means if is a marker of hundreds of different behaviors. women have changed certainly in western societies in terms of their life experiences over the past 100 years. we are all reaching puberty earlier in life. and that has been happening for the last 100 years. and we know that ms disease activity in women is very influenced by the activity of hormones. so these are all clues but currently we don't have the answers. >> this is just remarkable it has to do with research. it has to do with the hope for cure.

it has to do with gender difference it has to do with genetic implication it has to do with environmental factors. if you want to say give me a disease that reflects all of the dilemmas and opportunity and hope for medical science, this is one. >> absolutely. >> there is an i decisional about the four people around this table and that is steve-- academics, al is for the biotechnology company. and this kind of discussion would have been practically impossible what, 40 years ago. quite recently. academics by and large stayed away from pharmaceutical companies. it was really biogen and its genentech that opened this whole thing up. and it was really in the context of biogen that walter gilbert the first chairman of the advisory committee worked out the ground rules that made academics comfortable working with biotechnology companies. and that is revolutionized

not only the academic life of people because you learn a lot by working with a company. but also the capability of biotechnology companies of getting the best talent in the world to consult to them. >> as bill gates used to say, put more iq on the problem. finally, i always do this at the end of the day, and we have many that have jt sprinkled up in the conversation what is the one question would you most like to know the answer to? >> he meaninged-- mentioned it earlier, i would like to know what begins, what triggers ms at the very beginning. >> same for you. >> steve has taken that i will go for the understanding the biology underlying progression. >> rose: so what starts it and what makes it progress. >> mine would be the trigger, to figure that out. because i know that i have history in my family. but i know that that is not determinive so i want to know what was it about my experience. >> rose: mine with:. >> .

>> mine would be can we actually repair the brain. and you know there are these inhibitity ory proteins that no only prevent myelinatn but prevent axonnal regen raise, why they are there in is not clear. maybe they were important in development. but they are maladaptive when you have diseasement but if can with repair the central nervous system and we know it happens in the aftermath of stroke or spinal cord injury and ms is to exception. but if we can repair the central nervous system and we're just starting phase two trials with anti-lingo later this year so, we may know the answer to that very soon f we can do that i think it would just open up neuroscience to a whole newera. >> why do women get so much more frequently than men and what is responsible for this enormous increase in incidence in the disease. this is happening wit with-- depression is on the rise. what cosmic factors are determining the incidence of

the disease, that is a fascinating question. >> rose: i thank each of you. this has been remarkable. as i said it is almost a classic case of the kinds of things this program has been in of. you know, question, genetic influence. how it begins, how it progresses, what triggers it individually. can you, in fact, repair the brain and understanding the environmental factors and why they differ among gender and perhaps regional, you know, geography and other things. so this has been most destructive for me. what will i learn next time. >> my trovic lateral sclerosis, a disease that affects one cell time, motor neuron, lou gehrig disease, fascinating disease also. >> thank you for joining us. we will see you the next episode of our brain series 2.

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