ree-- charliest rose was provided by the following: >> rose: additional funding provided by these funders: 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 disorders of movement. they're associated with changes in the brain cells that help us move. these changes can affect the speed, quality and ease of movement. the two disorders we will focus on are parkinson's disease and huntington's sease. parkinson's disease was first described in 1817 by the british physician james parkinson. approximately one million people in the united states alone are afflicted. parkinson's onset is typically subtle and most commonly develops between the age of 55 and 65. its cardinal features include tremors, difficulty moving, slowness of movement and muscular stiffness. symptoms result when nerve cells in a part of the brain that produces dopamine fail and deteriorate. there's currently no cure for parkinson's disease. huntington's disease is much more complex than parkinson's. it affects a more diffuse area of the brain. it is a hereditary neurological disorder first described by the american physician george huntington in 1872. individuals with the inherited mut ant gene typically see the first signs of illness in early middle age. like parkinson huntington symptoms develop gradually over time it causes a progressive degeneration of the cells in the brain and slowly impairs a person's ability to walk, think and talk. there's currently no cure. tonight i am joined by two people without deeply understand parkinson's and huntington's. sam posey is a retired race car driver an a television commentator for abc sports. he has had parkinson's disease for 18 years. allen goorin is a retired physician and professor at harvard medical school and dana-farber and children's hospitals. at age 59 he was diagnosed with huntington's disease. they will each share their personal experiences and insight into their conditions. also joining me a remarkable group of scientist, stanley fahn, he is a professor at director of the center for parkinson's disease and other movement disorders at columbia university medical centre. anne young is a professor at harvard medical school. stanley us werein certificate nobel laureate and runs the institute for neurodeagain rattive diseases in the university of california, san francisco and once again my cohost is dr. eric kandel. and a ho word hughes medical investigator. >> we can discuss parkinson's disease and huntington's disease, two deagain rattive diseases of the nervous system that affect movement. what is interesting about these disorders is their history. if we consider autism, which is a program we did recently, that was discovered 60 years ago. we have had beautiful, detailed and insightful descriptions of parkinson's disease and huntington's disease that go back over 150 years. james parkinson in 1817 described six families that had what he called shaking palsy. the three defining features of the disease are that they have a tremored rest. they have an abnormallal posture and they have muscular weakness. this description was so detailed and so excellent that physicians soon were able to characterize the disease and see exactly what parkinson's saw and they renamed the disease from shaking palsy to parkinson's disease. but it was a long time before we began to understand what some of the mechanisms underlying the disease was. it was only around 1960 we began to realize the disease is caused by the fact that there is a depth of dope minnick neuron, dopamine is a mad you la tore system in the brain that affects the striatum which is a key structure involved in motor coordination. we now know that a lot of the treatments that are available for it are based upon this initial deep insight. huntington's disease was discovered 50 years later, about 1870. george huntington a columbia trained physician, very astute had the insight looking at families in long island that there were, it was a hereditary disease that he encountered which also affected motor movement. and the defining features of that were that it was genetic. hereditary disease, number one. that number two, there were involuntary movements and number three that it went beyond the motor system to also affect cognition and sometimes alterations in personality. the clinical picture alone suggests this disease goes beyond the striatu am m, it also involves the cerebral cortex, the epicampus in memory storage and sometimes thiper thalamus and cerebellum. progress in this disease also is very very slow and it was really until about 1968 that one began to make progress in it. and this owes a great debt to the her ted-- hereditary disease foundation which milton brexler founded. he was a very well know psycho analyst living in los angeles whose wife had huntington's disease so he started a foundation with a double purpose in mind. one is to get resources to do basic science. and the other was to try to direct the science in a productive way. and since this was a hereditary disease, the key idea was to try to define the gene that was responsible for huntington's disease. this was in the early years of trying to do gene sequencing and gene chroning. so this was a very daring effort. in 1983 they were able to localize the gene for huntington's disease to chromosome 4 to the very tip of the chromosome. an international consortium of gene hunters formed and in 1993 they isolated and sequenced the gene. that was an enormous advance because with the gene they could pop it into mice and into flies, and into worms and study mechanisms of pathogenesis. how the gene does its harm. and they learned an enormous amount about this. more over as they began to look at these disorders, they realized that in addition to the clinical similarity they both affect motor systems and they both share certain anatomical features in common. there also is an interesting similarity in the way the proteins that are involved in the disease become abnormallal. they realize this is a protein folding disorder. and that it belonged to a larger family of protein folding disorders which were pioneered by stand passner. he described jack object cry field disease as a difees-- we now realize that in addition to that, alzheimer disease that you and i talked about, front to temp oral dementia in addition to parkinson's disease, and huntington's disease are pro phone folding disorders. what does that mean. that means prot teen can exist in two confirmations. one is the normal confirmation in which it does its normal physiological function but it flips into the abnormallal confirmation t forms aggregates and these bundles of proteins are toxic. they kill cells. more over, they also release by the cells, taking up by other cells and in turn these aggregates kill the cells that take them up. so this is a way of propagating the disease, extending it throughout different parts of the nervous system. that is a profound insight, which allows us to think that there may be a unifying theme connecting these disorders. and perhaps allowing us to get a completely new therapeutic approach to this. so we are going to have a really terrific opportunity to discuss this. because not only do we have as you pointed out sam and allen here who have the disease but they brought their physicians with them. so stan fahn is a pioneer in parkinson's disease and anne young a pioneer huntington's disease. one of the early people involved in the disease foundation. and stan, of course, was the guy without has been thinking about protein folding disorders for much of his mature academic career. so we're in for a terrific program. >> rose: let's begin with stanley fahn and talk about a clinical introduction to park inson. >> the second most common neurodeagain rattive disease that we have, alzheimer alz most common, then parkinson. so most people have heard of it. muhammad ali has park inson, many others like michael j. fox and so forth. park inson's begins very slowly. it's insidious in its onset. the most common symptom that people recognize is the tremor. and the tremors are usually the fingers. in addition to tremor, there is the stiffness of muscles with the neurologist call rigidity. but probably the most important first symptom is something called slowness of movement and decreased amplitude of movement, difficulty turning in bed, getting out of a chair, swinging an arm when they walk, writing, their handwriting becomes small. and slow. they may have trouble shaving. and the tremor of courses interferes too but it's the slowness of movement that gets them. but the disease doesn't stop there. those are the early features. eventually a person's posture changes. they become flexed. so they have astute posture. in fact people recognize james parkinson's thesis recognize the posture of pain people with parkinson, bent over, their elbows are flexed. and walking is involved. they begin to have a shuffle of their walk. their balance becomes impaired. if they lean over too far to one side they can fall. so falling becomes a problem in more advanced parkinson's disease. and then a particular problem is it's not everybody gets, is freezing of gait, that is their feet stick to the ground so they start to walk and their feet are stuck before they can walk. often it happens when they are turningment so this leads to falls. parkinson's again is a deagain rattive, a little unusual in that it does tend to start on one side of the body but eventually it does go to the other side. so it does progress. >> rose: sam posey, tell us what it is like for you to experience parkinson's and how you first noticed it. and how it progressed for you. >> well, i'll tell you t was like being ambushed. i was just turning 50 and everything was going incredibly well in my life. hi a great job with abc sports. and suddenly out of nowhere comes this tremor, and stanley just described it. in my case it was the wrist and there was no hiding it from abc. i lost my job within a few months. but it progressed so slowly that it was a strange sort of dichotomy. because here is this thing, no known cure, everything, everywhere i looked t looked like a nightmare but as i said, it progressed so slowly that now 18 years in, i can still describe it largely as an inconvenience. it's a hell of an inconvenience. i mean i can't do buttons, i can't change light bulbs. but it's a-- . >> rose: . >> you can still race cars. >> driving and panting have been the saving grace for me. because something about driving, all of th the-- parkinson's symptoms vanish when i'm around my racing car. >> fantastic. >> rose: what does that say. >> i think what it iss basal gang leah is bypassing you. you are working out of your cerebral cortex like in sleep the symptom goes away with sleep. people ask why. but i think what it is the basal ganglia are not being used. when he is stimulated up driving he's concentrating and focusing, he has to use his cortex. >> rose: you also saw psychological help, did you not. >> i did. a friend of mine said you should get yourself a psychiatrist immediately and i did. there was a local man, sandy morabli who stepped up to the plate and has been fantastic for me ever since. the point behind having a psychiatrist i think, well, another member of the team. i look at this as a racing team, really, assembled stanley is not, this is no demean, he's the chief mechanic. >> but my sky test, was, the original purpose was because there would be things that would drive me crazy about this disease, that it would be just better not to be taking out on my family. >> rose: what about longevity? >> well, this, of course, is something that scares me to death, the eternal silence as tenison would have put testimony and whether that will be hastened by all this or what, i don't know. right now as i said earlier, 68 and feeling terrific. my general practitioner said you're in great shape except you have parkinson's. so i done know. >> rose: let me have stanley add to the history we were talking about. >> the history is fascinating. you mentioned that it was 1817 when james parkinson's described it. it took another 100 years, basically, before we knew anything more about park inson's. and that was in 1912 and 1917, two important papers on the pathology of parkinson came out. in 1912, frederick lewy describes inclusions in certain newerons in people with parkinson's disease. then in 1917, a russian, who was a medical student? paris studied parkinson brains and wrote his pain describing the sub standia niagara was involved. if are you look on the left you see a dark band on each side of the midbrain. this dark band is called the sub standia nigra, black substance, it contains a compound called neuromelinum which we know is derived from dopamine which is present there. what he found was decreased pigment. if you look on the right half of this graphic you will see a parkinson brain and there's decreased pig am. if you look under the microscope, you'll see that there is a cell loss in the sub standia niagara, but not only that but he also saw the inclusion that lewy described. and he called it lewy body. if you look at the graphic there. you'll see nucleus in the cell, and below this and to the right is inclusion called the lewy body. this is found within the cytoplasm of the cell and hallmark of the disease. the next part of the interesting picture of understanding parkinson's disease took about 40 years. carlson actually discovered dopamine in the brain. found high concentrations. he was very much interested in what we call monoa miy, since he was interested in what caused drug induced parkinson from reserpin, a drug from india, it caused people in animals to become parkinsonian no one knew how that work. but early investigators found a decrease in serotonin. he was interested. i wonder if it decreases dope minute. he gave to animal and showed a decrease as well as serotonin. then he said which one is it. so he took rabbits. he injected reserpin, made the rabbits listless, droop, couldn't move, their ears dropped down and then injected the precursor for serotonin, nothing happened. injected the precursor for dopamine which is l-dopa and the animals woke up. carlson recognized, this is very important, and he came up with a hypothesis that dopamine is somehow involved in parkinson's disease. he came up with this hypothesis in 1959 and eventually he won the nobel prize the same year that eric won it. >> okay. anne young tell me about huntington's. >> huntington's is a little different that parkinson's but it starts insidiously just like parkinson's. it begins in midlife. so usually after people have had their family,. but it can start in as early as age 2 or as late as in the 90s. so there's a vast-- . >> rose: as late as the 90s. >> yes, i've seen a person, 94 with early huntington's disease. and the disease starts out with little personality changes, perhaps some changes in cognition. and little flick-like movements of the fingers and toes that people term korea or dance. as they move along in the course of the disease, those movements get really quite severe. and people lose their fine motor coordination, and eventually actually need to have total care. they can't speak. they can't swallow. they can't walk. and it's a long illness that takes place over 15 to 25 years. and with allen in his family, allen inherited the huntington gene from, here he is, the red square is depicted as allen. it's red because he has huntington's disease. and his mother, the red circle also had it. and she passed it on to him. and her mother, his grandmother. >> rose: there is a clear genetic basis. >> clear n huntington's disease it is a clear inherited disease, passed from one generation to the next. and what we call a dominant fashion. >> rose: let me turn to allenment. give us the sort of real life experience with living with huntington's. >> yes, i've been very fortunate that i don't have as much motion disorder as a lot of people with huntington's disease do. so i still ride a bike 20 miles on monday and 30 miles on wednesday. and try to exercise every day. i thought i was free. my mother got it in her 40s so when i turned 50, we celebrated. we built a house in martha's vineyard and we were really on the way. and all of a sudden at 59, i developed symptoms. >> rose: what were the symptoms, a tremor things that we described. >> the symptoms were mostly insomnia for me. >> rose: really. >> i could not sleep. >> rose: an other symptoms. >> then also had some tremor and a lot of movement, i was crossing my legs a lot. >> rose: you were 59. >> yes. >> rose: did you seek help. >> i did. i saw-- because of the family history, we thought of huntington's disease and so i tried to get the test done and i went to my doctor who said no, you don't have huntington's disease. you're too old. i said no-- i said though, no, i think i have huntington's disease. so i finally convinced him to do the test. i tried to, i paid for a test myself. and sent it off. and they never did the test on me because i wasn't approved by a doctor. even though i was a took tore, they wouldn't accept me as a person to authorize it. >> rose: how are you today. >> i'm doing really well. i think, you know, the creatin has really helped me. i started taking that when i was 60 or so. and i think that has really made a difference in my progression. >> rose: as we did with stanley and parkinson's give me the sense of the history. >> well, as eric mentioned earlier, huntington's disease i think some of the major breakthroughs in huntington's disease have been through advocacy and philanthropy, actually, from the hereditary disease foundation and other foundations. and one of the important things is that that was organizing the effort of all the scientists to work together which was really unique to bring people to bear on this problem. and huntington's we all have a huntington's gene. all of us do. there is a portion of the gene that gets bigger in huntington's disease. and that expansion gives you disease. so what happens in huntington's disease is that the code is altered, the genetic code. now the code of the genes is, our whole genetic code is made up of an instruction manual, basically. and four letters is the alphabet of the code. and then there's three letter words that are made up of this code. and each three letter word codes for an amino acid and a protein. and what happens in huntington's disease is that one code, cag, gets repeated again and again in a portion of the gene. now we all have in the portion of the gene cag repeated multiple times. but what that results in, each cag results in a glutamen in the ultimate proteinment so every time you have a cag you get a glutamen. and in most of us, those gl, tamins are functioning in the protein. but what happens in huntington's is that gets expanded. and when the number of glutamin's gets expanded in the proteins that confers a toxic property to it. and that causes cell death and aggregation. so what happens with huntington's disease is that if you inherit more than 39 of those cags, you will get huntington's and allen got it at 59. >> rose: so if are you more than 39 are you a high risk or will you definitely get it. >> you will definitely get it if you live long enough. >> rose: yeah. >> if you inherit fewer than 35, just think there is only four difference there, if you inherit less than 35 you will never get it. >> rose: no risk. >> but what is wonderful about this insight is that it turned out that this is not unique to huntington's. >> that's right. >> -- it occurs in other diseases as well. >> exactly, so it turns out that after this was discovered there are maybe ten diseases that have this cag expansion. they all affect the nervous system, curiously. and they all cause neurodeagain rattive disease. so we think that this toxic portion of these glutamins in the protein is bad for you. and you have the nucleus of the cell, the protein is made in the next slide and the protein in the cell, body in the cytoplasm outside the nucleus is then processed. it's chiefed in two. and the pieces that are generated from that then accumulate in the cell if you have the huntington protein with the expanded repeat. and you can see that in the process of the cell, as well as in the nucleus. and that causes disrupted cell function and cell death. and we know now enough about the process that i think we can make a difference in treatments for the disease. >> rose: stanley, help us understand the mechanism behind these disorders. >> so the meck nichl-- mechanism we believe now behind these disorders really begins with studies of a very rare neurologic disease called creutzfeldt jack object disease. about one in a million people get the disease. you can describe it as alzheimer disease on fast forward. so the brain degenerates from the first symptoms until death within 3 to 6 months whereas in alzheimer disease you get a profound dementia but it takes ten years. and we're talk approximating about even slower problems with parkinson's and huntington's. i was looking for a virus that would cause creutzfeldt jakob disease because four years before i began these studies the disease had been transmitted into monkeys and apes at the nih. and i kept looking and looking. and there was no virus. there was no genetic material of life. dna orr na. there was only protein. and as i began to investigate this further and further, first identifying prot teen with a large number of colleagues, helping me, then it became clear that the protein was changing its shape. it's quite clear now that different proteins cause different diseases. we've been hearing about parkinson's disease. we've been hearing about huntington's disease. and you see this little chart in which there are six different diagain rattive neurologic diseases, each one has a different protein. but in each case we now believe that the protein is changing its shape or confirmation as scientists talked about it. and in some cases in the nucleus, in parkinson's disease the nucleon a different protein. it aggregates and it forms the lewy bodies that we heard about. so now beginning to piece this all together, and it has huge implications for how we develop therapeutics. >> it also points out something which one didn't realize before. how this disease is propagate from one structure in the brain to the other because these toxic aggregates are released by cells. they're taking up by normal cells and these normal cells eventually become infected, if you will, and they ultimately die. this is an extremely profound unifying insight that just really crystallize out in the last few years, with the detail that we now understand it. >> sam, when you look at the scientific discoveries, how big benefitted patients? >> well, of course i have been so lucky. i phone i feel as if stanley has been able to roll a carpet out in front of me. you know as it gets worse the treatment gets better and better but my own approach has been, woody allen once was asked what he believed in. and i think they were looking for a religious answer. but he said i believe in the powers of distraction. and i pursued that religiously because i go on with my painting and my racing and everything else. and i get up in the morning as somebody that doesn't have parkinson's. i mean i'm surprised at things that i can't do, but they still fall in the category of inconvenience, as i said earlier. >> what do the paintings look like. >> the first one is of a hotel in florida. i made that in my mid 40s. it's part of a group of landscapes i made them. if we look at the next one, these last two are very recent. i've been painting from a model. >> marvelous. >> and talk about going from out of doors where people swarmed around you to the seclusion of a studio. it's interesting for me to trace a little bit the developments of parkinson's and see how they interact with the painting. i mean there are times when i can hardly paint at all, my hands are shaking so badly. and i have to give it up. then there are other times that are almost clairvoyant so there is a strange relationship between parkinson's and creativity. >> what is interesting that you said about you getting into the car and you feeling completely normal when you drive, is check close who-- was with him when he had alzheimer disease and he side he walk around, his memory would be defective in things like this, he walked in a studio, he was like a different person. and you know, he continued to paint until almost the end of his career when he had advanced alzheimer. >> well, look at woody guthie, he was incredibly creative, and you know, many people with huntington's are incredibly creative. and have done lots of interesting things. >> rose: stanley, let's compaq and talk about some of the approaches to parkinson's start with the park could logical. >> sure. well, i mentioned already carlson discovered dopamin dopamine-- and came out with the hypothesis. and so the next step was to find out how does one follow up with treatment. one of the things that you can see in this graphic here is that the dopamine was then found to be found in the cells of the sub standia nigra and moved up to the striatum. and now we can measure in life and we can see that, if you have an pet scan this measures essentially f-dopamine in brain so this is a precursor of f-dopamine and lights up the dopamine nerve term calls-- terminals in the brain. and this is a normal brain, it is lit up with where the red is. as parkinson's starts to develop, you get a mild degree of parkinson's symptoms and a mild loss of the pet scan uptake and the post ter yar part gets affected first. next we see as more advances, a moderate disease and then finally, in more advanced disease you get almost complete loss of the dopamine content so we can actually see a living person, and i think sam had a pet scan and he saw he had some deficiency of dopamine at that time. >> yeah, the technician said here would you like to look at this thing. and he pointed to a normal brain and then he pointed to mine. and the shock of seeing that your brain doesn't look normal is profound. and i mean it's really abnormallal. one of those lobes is there and the other one just wasn't. and i must admit that was part of the early phase of depression and the shock of the getting the disease and everything. it really overwhelms you at first. and one of the things i think i feared the most which i don't think has happened, but was the loss of identity. you feel that this disease is going to attack you as a person, somehow. and disrupt the core of your values and your sense of yourself. and that looks at that pet scan seemed to threaten that tremendously. >> that reminded me rick of a friend of mine who you know who was suffering from terribly terminal brain disease and he said to me once i'm not, i don't feel like i was the person i was. he saw himself as a different personality because of this. >> well, what we have fortunately for sam and many other people with parkinson's disease is a good treatment. l-dopa now is the gold standard of treatment. after it was found a decrease in the brain of dopamine many neurologist try to give l-dopa as a treatment. we know today you need high doses anlong-term treatment several weeks before you can get better. the person who was able to find that was george kotchett. and so the paper was reported in 1960. it was 1967 that george kotchett found a way to do it. and he was a physician working at brookhaven national laboratory on long island and he started to bring patients into the hospital and give them small doses of dopa and build the dose up gradually overtime avoiding the nausea, vomiting. and when he hit a big dose for a long period of time like that, miraculous this was a revolution of treatment in neurology. they got out of the wheelchair, they walked and can do all kinds of things they couldn't do before. >> rose: what about deep brain stimulation. >> that came into being because people already knew from prior surgical experiments that they can target a certain region of the brain and reverse some of the symptoms. so but a neurosurgeon in france decided instead of a lesion let's do a deep brain stimulation as the target so first target was globbus palbus because that was known about, and that helped. and then eventually the nucleus became the target because that was even more effective. and so with the stimulus electrode put into the target and turning it on, then they can-- this is what they call inhibity the overactivity of the nucleus and reduce the symptoms. >> rose: ann what about huntington. >> huntington's as you know is more complicated than parkinson's. and i think the first thing that scientists began to do after parkinson's and dopamine was discovered is they said let's look at other diseases. so they looked for the missing chemical and didn't find it. and right now our theerpees are really gauged on the basis of what we think the protein is doing in the cell. none of our therapies can reverse it. and none of our therapies can slow it down as yet. but we can in animals. so for instance, we know now that we can make animal models of huntington's disease. and actually, not only stop it, but we can actually reverse some of the symptoms of it. so we think we'll be able to do this in heims. and we have therapies that we're trying in humans. one of the things that is important to realize that's different about huntington's than parkinson's, and this is in large part due to work with the hereditary disease foundation and actually the daughter of milton wechsler, nancy wechsler. she's at risk for huntington's because her mother had it, she's devoted her life to finding the huntington gene and a therapy for the disease. and once the gene was found, the hereditary disease foundation has been working on new therapies for the disease. and we think that we can alter the progress of the disease in people at risk, so we now know that we can test people, unlike parkinson's we can test in huntsing ton's disease to see who inherited the gene. and actually think about starting people on therapy before the symptoms even begin. so allen, for instance, we put him on a therapy called creatine which is an energy booster. it improves energy, function in the brain and he's been taking massive doses of it. you started at one point you got up to 30 grams a day. >> i'm still taking it at a lower dose at 12 grams a day. that seems to be doing fine. >> he has had a marvelous career as an extraordinary physician, treating children who have bone cancer, developing more kinds of therapeutic trials by combining different therapies, a marvelous career which unfortunately he was not able to continue. but he still advices the dana-farber in boston as to how to think about these things. so what is wonderful about these two characters is that they've got severe disease but they're functioning amazingly well and continuing to contribute to society. if you are painting is considered a contribution to society, we'll have to discuss it another occasion over a glass of wine. >> something i have learned through the years is how incredibly helpful people are. i mean i am really very reliant now on people for help of all kinds from doing buttons up to all sorts of things. and i mean just coming to the studio this afternoon, i started to fall right on lexington avenue and a big strong man picked me up. i mean dusted me off and sent me on my way. >> sent you on your way. >> it is just remarkable how generous spirited people are. i mean i have been in airports and my hands have been shaking too much to get my wallet out of my pocket, you know. >> there was a pickpocket. >> exactly. you always have to worry about that. >> rose: let me turn to stanley, and then we'll have a general discussion her and talk about some of the general treatment strategies for protein confirmational disorders. >> so i think the important thing to realize in all these diseases is that we have therapies, but they're symptomatic therapies and that is what l dopa is as stanley made it so clear. but the underlying disease process marches on. and as eric said, it marches on by accumulating preons within individual cells which then spread to neighboring cells. and then more and more spread occurs. and it's true of all these diseases that we've talked about. parkinson's disease, alzheimer disease, toronto temperal dementias, chronic traumatic encephalopathy, aldz alz, als, motor neuron disease and hunting-- huntington's disease. so we've got to get at these proteins that are turning into preons and stop them. i've marked three posh intervention points. so one is that we decrease the normal precursor, protein. the second one is that we interfere with the change in shape from the normal precursor to the preon form. and number three, is that we increase the clearance of the preon form. that we get rid of it and when we get to a point when the level of the preon form is low enough, we don't have to get it to 0. but we need to get it down fairly far, in some people. and then at that point, the normal clearance mechanisms take over in the brain. so we can think about this in a very different way than we did initially. one is i think the therapies can work for a few weeks or a few months. they need, they can be short term. they don't need to be years. and if we have to go back and retreat somebody, that's fine. and so you spoke about, anne spoke about the diagnosis of hunting ton's disease and having a genetic test for this. but i think in all these diseases we're going to need very good imaging techniques. and we saw this with stanley's demonstration of what goes on in parkinson's disease with the flora doma scans. we're going to need this for every one of these. and we need to be able to follow these proteins. we have to look at the precursor form. we have to look at the preons when they're small aggregates and then we have to look at the large aggregates, the fibers. so this is a very important new approach that goes way beyond creutzfeldt jx jakob disease and really the whole spectrum of neurologic diseases. >> rose: it sounds to me like we are at sort of an influntion-- inflection point here. >> absolute turning point. for example, one of the interesting things that emerges with this is why do these diseases occur with age. well, one possibility of course is as you indicated, the aggregate itself perpetuating form develops but parallelled with it as people age, the clearing mechanism that is capable of getting rid of it may very well weaken. and if we can find out the nature of the clearing mechanisms we might be able to reinforce them just like your strength is being restored by creatine, we might be able to find some way of doing it. i think this is really the first time we're getting an insight into a whole family of disorders, that if we could solve any one of them in a fundamental way, we would revolutionize neurology. >> if we could find a way of getting rid of these aggregates, either preventing them from forming or allowing them to form but inhand-- enhancing the system that gets rid of it, we could be did --. >> rose: we're looking at a revolution. >> we're looking at a revolution. >> rose: can reverse it. >> i think in animals we can reverse it we ought to be able to do it in humans. >> rose: that within extraordinary. >> not to the point where i think if you looked at end stage disease, maybe not. but in moderate stages of the disease, there are six cells but they're not dead-- sick cells but they're not dead and we can rescue them. >> rose: correct all of them, all the things we talked about so far, ann and stanley and all of you. some sense of how what's possible in terms of the future reversing the diseases of the brain that we've discussed. >> i think that what we need to do is identify the markers that tell us whether somebody is going to get the disease. so you will go to your local doctor and get a little test and it will say you may be at risk for huntington's disease or parkinson's. and then you're started on a program of therapy if you are at risk for that disease and that therapy will take place over the rest of your lifetime to reverse the symptoms. the huntington's gene really started the work on the human gene only project. i mean it was one of the sort of place markers of saying if you can do there in huntington's, you should be able to map the human genome. >> before mapping the human genome they discovered the gene that caused huntington. >> exactly. >> the mere fact you could develop a methodology saying here is aye gene, we haven't the fog just notion which chromosome it is on, they could localize the chromosome. and then sequence the gene and see this cag repeats that showed you related to other diseases as well, was a profound revolution. in fact, i would say we should go back and say that a lot of this due to watson and crick. i mean modern molecular biology has absolutely revolutionized medicine. it takes so long to go from insight to cure that people are disappointed we don't treat all of these diseases. these are enormously difficult problems. >> the gene hunting technique for huntington's was also applied to parkinson's subsequently to that. and we now have been 18 different genes that can cause parkinson's. the first one was extremely important that was the one that mapped alpha sin new clean that found to the just in the sub standia nigra but many other parts of its brain. it starts in the lower part of the brain stem and progress up over time. the dark brown at the bottom, is the medala and that is where the alpha new cleese aggregate accumulates, up to the pons is, and in the next slide up to the cortex so you get other symptoms and it is because of this spread, of the deposit of the lewy neurites that is what they are called, you get symptoms of parkinson's. >> rose: are you optimistic? >> i'm very optimistic. but it's very difficult. i think it's difficult for several reasons. one is as eric said, not a single disease has been cured yet so we don't have a simple road map. on the other hand, there are several factors that make it very difficult. and that first, the first factor is called the blood brain barrier so this is the barrier from getting things in the blood, into the brain. and so only small molecules can get into the brain. so it limits the sizes of our medicines that we'll be able to develop so we have to be very clever about developing something which is very small. and i think we also now are beginning to learn with these insight that all of these are preon diseases, that we're going to have to get these medicines all over the brain. so just trying to put them in one tiny place is not going to be good enough. on the other hand, as you saw with this pet scan i think it's going to give us when we develop the right probes, and reporters as they're called, for each of the different preons because each disease there's a different protein turning into a preon and we can begin to measure the normal form, the preon form, the aggregated forms, when we can do that, we can diagnose the disease like ann was talking about very, very early. before there are symptomsment you can imagine a day when you're 50 years old and you go get a physical exam and you lie down in the pet scanner and we can look at all these proteins simultaneously. and we can see which ones are turning into preons. maybe it's one. maybe it's two. that will inform us about what medicines to give either stimulate clearance or probably to stimulate clearance and cut down the prekers-- precursor level and cut down the conversion. medicines will work at all these different points. and when we're able to do that, we'll be able to stop the disease, i think, three or four weeks, not months, not years. but to be sure, we'll then rescan the people's six month later or a year later. and if they need more medication, we'll do that. so i see a day when this happens but it's a long ways unless we get more push. and get this done. >> also, one of the things that we know in huntington's disease and we should be able to apply it in other diseases is that we can actually clip the gene, the messenger rna for the gene. so you can target the actual huntington gene with these little trick pieces of rna. it comes in and it binds to the gene that you're worried about. and the body says below, that shouldn't happen. and in come the scissors and clip the gene and target it directly so that you can turn the gene for the disease specifically off just like a silver bullet. again, we can do it in animals and they're planning human trials to do this, in the next couple of years. so we'll see what works. >> rose: i always like to ask this question and i think some of you have answered this. what was the one question you most want to see answered, sam. >> well, i want to know what the hell is causing this so that it will come out into the open and i can fight it. instead of the shadowy adversary for so long. >> rose: the joy of this conversation is that there are a lot of very good people in search of that. >> i'm thrilled. >> rose: . >> absolutely, the same thing like sam wants, we want to know the cause and how can we stop the disease from getting worse. we're hoping that scientists like stan next to me will answer that. >> so my dream in all of this is that we are able to develop therapeutics over the next few years and early diagnostic tests so we can stop these diseases and which are only growing in number as people age. >> and live longer. >> yes. >> and are you hopeful. >> i'm very hopeful. >> allen. >> i would love to see a cure for my grandchildren and my daughters before they get symptoms if they have huntington's disease. that's what i would like to see. >> rose: . >> i would like to cure everybody with all these diseases. if i could contribute to some of that, which would love that but i want to see the cures. and it's not just in our country, but it's all over the world. these are just-- horrible illnesses. >> they know no boundaries. >> and we need to take them to everybody. >> eric is. >> my hope as a psychiatrist, is i wish we had the insight of the psychiatric disorders that we have in the -- this is a remarkable set of insights. 9 fact we can't cure it is tragic but its progress in the last 50 years has been spec tack are lar recall and my hope is in the next 50 years we'll have you and i 50 years from now will be meeting to discuss psychiatric disorders. >> let me conclude by saying a couple things. number one is that i'm so leaply hon ared to have people here, who are both living with disease and in hot pursuit of disease. with a sure commitment that with overwhelming desire to fine answers and to make them applicable disease, they are in one of i think, one of the great journeys of life. and people like those who sit with me today, you know, offer and for those of you who are thinking about how you can make a difference, science is a place that you can make a difference. science is a place where you can take vastly expanding tools, and go and search of some of the most interesting questions with some of the most extraordinary consequences. so i thank each of you for coming here to share these insights and these experiences. and i think we're all better for that. and we understand that the great possibilities of understanding about this brain of ours and what its implications for both disease and health are. so thank you for joining us. we will see you next time. but before we go, i always ask eric to tell us what's next. >> you toll me you wanted to do multiple sclerosis next so that is what we are going to do. a different disease, also degenerative disease to the brain. we have very good insight and treatment so we'll have a very good session next time. >> thank you, eric. thank each of you. great to see you, ann, thank you, allen, thank you, sam, thank you, sam, and stan, and thank you for joining us for this episode of our brain series 2, see you next time. captioning sponsored by rose communications captioned by media access group at wgbh access.wgbh.org >> the series is made possible by a grant from the simons foundation. their mission is to advance a fron tears of research in the basic sciences and mathematics. >> funding for charlie rose has been provided by the coca-cola company, supporting this program since 2002. >> and american express. additiona funding provided. >> and by bloomberg, a provider of multimedia news and information services worldwide.