Breakthrough Medicines for Serious Brain Disorders: Jeffrey Conn at TEDxNashville

Wow how do I follow that what a performance and what a day this has been just a tremendous day I've been inspired and have gained so much from the talk so far I I'm a neuroscientist and I have been studying the brain now for all of my career since college days I think all of us when we think about the brain we share the sense of all and mystery and and are just amazed by the power of the brain and how it defines us in so many ways how it determines who we are our personalities our likes or dislikes in some mysterious way that we don't fully understand tend to be housed right here but the other thing that's that's so important that I think we're all keenly aware of is that nothing is more terrifying than when things go wrong with the brain so when the brain begins to this to miss function and we begin to have diseases that are associated with that that's something that I became very keenly aware of very early in life with a very close friend who I spent almost every day with fishing hanging out doing a lot of a lot of things but Bailey was with this close friend and one day he have been during our teen years I got a call from his parents they were frantic because he had disappeared wondering where he was and I had no idea I had not seen him but when he was found he was wandering around incoherent and out of touch with reality and he had had a psychotic break which was the beginning of a lifelong struggle that he had from which he never really recovered of schizophrenia so as a very typical incidence of schizophrenia with that adolescent onset and an absolutely devastating disease but overnight I saw my friend come from a very engaged person that I spent every day with - a person that I could not connect could not connect with me then there were other individuals like my baby sister clearly my best friend as a child we were tight growing up spent as much time as we could together I and when she hit her teen years she started struggling with severe depression and that depression lasted for the rest of her life and actually ultimately led to problems with substance abuse as she was trying to treat that depression and finally took her life at a very early age so these things give a very strong reality to the power of the brain and the power of dysfunction of that brain and then there are other recent examples like my mother-in-law shown here in the left this was a a picture taken only six or eight months before she died of brain cancer she was treated here in Nashville by Reed Thompson who was at this event last year I grant my father in in the middle there with my children and my sister Melody's son who was a brilliant man who spent the last years of his life struggling with Alzheimer's disease before he passed away my great-nephew Chi shown here who struggles with an autistic spectrum to disordered living here in Nashville so we see these examples and these are examples that are very real-life examples of the power of the brain the impact that sometimes devastating impact of disorders but the thing that I think we all know that all of you know is that this is not my story this is your story this is a story that I think is shared by everyone on this earth and and if you think of the diseases that we're thinking about and talking about Alzheimer's disease Parkinson's disease Huntington's disease schizophrenia depression bipolar it goes on and on chronic pain disorders whether it be back pain or some injury neuropathic pain these diseases are impacting literally millions of lives and if you think of those diseases isn't a thousand other diseases of the brain that I haven't had time to mention I think that every one can think about somebody that you know and you love that is impacted I'd like to have you raised your hands if when I named these diseases or one that I haven't named if you know someone who's struggling with with one of these brain disorders I just like to see a raising of hands to see how many lives here that has impacted and I think what we can see is just about everybody in this room is impacted there none of us that are immune from this and if it's not happened yet it is likely to happen at some point in our lives so the good news is that we're at a place today in science where we understand the brain we understand human disease at a level that it's unprecedented I couldn't imagine 10 years ago being where we are today in terms of our understanding we now have a complete sequence of the human genome every potential drug target in our body the sequence is known we now know the genetic variation of individuals and individual cases of diseases are becoming more and more clear so that theoretically we can target medicines for an individual and their disorder we now have an ability to image the brain and look at activity of the brain in disease patients and see what has gone wrong and from that understanding begin to think about new medicines the problem and and what's discouraging is that this tremendous increase in our understanding has not translated into the medicines that we so desperately want to see appear and become available for for treatment if you look at the medicines now available the FDA actually lists over 10,000 medicines that have been approved for use in the US so when you go to your doctor it sounds like a large arsenal of medicines that are available for that treatment but when you look more closely at this what you'll see is that these 10,000 medicines actually are represented by only 433 distinct chemical substances and what you have is different combinations different formulations acetaminophen the active ingredient in Tylenol is in almost 400 of these medicines for instance and so it really narrows down to a very small number of medicines available and most of those are many of those were approved before 1950 before we had this tremendous increase in our understanding of human disease if we think about neuroscience of brain disorders the major antidepressants that we use were discovered in the 1960s and what we use today is still just a slight variant of those initial drugs for Parkinson's disease the mainstay of treatment is still a drug that was discovered in the 1950s and and the list goes on and on of relatively incremental advances that don't come close to tackling the issues that we so desperately want to see tackled so the question is why why is it that we have this large increase in understanding we understand the brain at a level we never have before and yet we are not able to translate that into new medicines and I can't go into the details of all the reasons but I think you can look at how medicines have been developed and begin to gain an understanding of just the sheer economics and the practical issues involved in taking that knowledge and translating it to a new treatment that at play a major role if we look at the classical approach to discovering new medicines that has led to most or many of the medicines that we have today and I think I dare say most of the medicines trace their roots back to this approach it was actually a very simple approach and that was that there were medicinal plants that have been in use by humans for centuries in many cases many cases millennia and we knew that those plants had medicinal properties and what we did was we took those plants as we began to understand chemistry and had the tools to do that in the 1800s Early 1900s identified the active component of that plant and then synthesized that component and we had a medicine so it was a very short path from identifying that molecule to having a new medicine that could be marketed we then began to make improvements on those medicines and so making modest improvements from those starting points new medicines began to appear the problem with this is that while it has been extremely extremely fruitful we've really mined this this gold mind that has been available to humans and if we think of the diseases that we're talking about today Alzheimer's disease Parkinson's disease diabetes different cancers the things that we all struggle with those are not diseases for which there are medicinal plants so we can't rely exclusively on this model so what we do today is we take a different approach that is critical in my view and that is that we devote tremendous energy and resources to understanding these diseases now understanding how the human body works and what goes wrong in a disorder from that we then develop a hypothesis that tells us that we might be able to develop a medicine if we target this molecule in the body or we develop an approach but that's a hypothesis so whereas the old approach started with the medicine we now start with a hypothesis and now we have to go through a tremendously expensive and difficult process of taking that hypothesis and moving it to clinical use well that process is extremely expensive and this just shows the steps in that process and I won't go through them in in this context but each step has tremendous risk and lead and there's a lot of failure but the ultimate cost of developing a new medicine with this new approach today is 1.8 billion dollars most of the programs that are initiated fail because of the difficulty of the process and those that do make it all the way to the market only three of ten actually bring in enough revenue to pay for themselves so it becomes extremely high-risk and from a business standpoint Thai there are some that argue that it could be unsustainable that's especially true in neuroscience where I many companies have stopped their efforts in neuroscience because the risk is so high relative to some other therapeutic areas so the problem with this is that there's a disconnect in my view between the traditional approach that we have taken in academic medicine and academic research and what occurs in an industry setting to make new medicine so traditionally research occurs in universities clinical characters and universities and companies take that knowledge that comes from the universities and translate that into new medicines that are then marketed the problem is that if you're working in a university setting with this model and you develop an idea you don't have the ability to move it forward and I just want to give an example of that this is an example with Parkinson's disease it's a paralytic disorder that leads to tremendous difficulties for the patients and this is a patient her name is Sybil who was at Emory University when I was on the faculty there and she was being treated with surgical techniques that took advantage of an understanding we had of brain circuits that were overactive and this is a patient in Bay Linda long and Terry VTech there and I just want to show you a video of how this understanding led to development of a surgical treatment so this is just pictures of her before her Parkinson's disease she and her husband immigrated from Jamaica and then at a very early onset age she develops Parkinson's disease was rendered virtually incapable of caring for herself so even simple tasks such as feeding herself dressing herself unable to stand unable unaided unable to walk without help and this is maximally effectively treated with the currently available drugs she then went in for surgery where where there was a surgery to reduce excessive activity in one side of her brain and you see this tremendous benefit of the surgery so she's now able to stand unaided to walk a tremendous gain-of-function but that didn't completely reverse it now after going in the other side of the brain this is the same patient Sybil who after the bilateral surgery and just a tremendous regaining of function Cybil last I heard when I last talked to Malin and Jerry is still doing very well it that was in 1998 she's doing extremely well and just a life altering surgery obviously for her I don't think I look at this video without either wanting to laugh or cry depending on my mood but very exciting the problem is is that Sybil and many other patients who received the surgery had to fit very strict criteria before they were eligible for the surgery and only a few centers in the world could perform the surgery so for people like Sybil it was life-altering but it was not available to the vast majority of Parkinson's patients so we began to think about this from the perspective of a medicine and began to think of ideas for accomplishing the same thing with the medicine that you could swallow it would get into the brain have the same effects on this brain circuit and have major advantages over existing therapies we spent several years doing that profiling looking for these druggable targets neurotransmitter receptors and ion channels we identified one that had all the properties we wanted the problem we had is we were in a university and there was no way to take that further to a medicine so I was so convinced that this was an approach that could work and I was not able to do that in a university setting and that was large part of what prompted my move to a major pharmaceutical company where I was head of neuroscience and thought that in that setting I could have the influence to try something fundamentally new like this the problem in the company setting is for reasons that I am sympathetic with they saw this as too high-risk it had never been tried the cost of investing in this is so high and and and it was just not something that even as an insider in a company we could get that off the ground and get the company and investors to agree to try that so I began to think this problem through and came to the conclusion that the only way that this will be solved on a broad level not just in this case but in every kake's is that we have to have translational efforts in universities where university investigators have the tools and equipment and the infrastructure normally available only in companies to take those ideas and move them closer to drugs with a major goal of be risking these efforts so that companies can afford to invest so I moved to Vanderbilt we developed the Vanderbilt Center for Neuroscience drug discovery and built all of the infrastructure that is traditionally only available in a major pharmaceutical company with one primary mission and that is to take advances in basic research and translate those to advances in clinical care so put the infrastructure in place so that we can accomplish that and then the risk investment in these in a industry setting the problem was there were no funding mechanisms in a university university funding occurs by a very established approach and this type of work was not funded so that was a problem when I came back to Vanderbilt and was very fortunate when the Michael J Fox foundation decided to take a chance Michael J Fox is another individual that I see is just a truly inspirational person his foundation invested in this approach gave us the money we needed to develop molecules to see if this approach would work and I'm happy to tell you that in September of 2011 we were able to announce that we now have drug candidates that are ready to move to clinical development for testing in patients based on this concept something that could have never been done in the traditional models and without the commitment of the Fox Foundation as well as the NIH the National Institutes of Health and their tremendous investment so very exciting and that's only one example we in 2011 announced two fundamentally new approaches to treatment of schizophrenia that have are now moving forward with corporate partners in for testing in patients and for an autistic spectrum disorder fragile X syndrome so this is very exciting in that it's the first it's kind in treatment of this type of childhood developmental disorder so I want to end by just telling you a story of another great nephew of mine his name is Wil he lives in the Chattanooga area and this is Wil at the Forbidden City will was born with a genetic defect that leads to disease called cystic fibrosis a very severe lung disease that ultimately over time will prob a patient from the ability to breathe will and his family were motivated instead of being defeated and began to invest in working with the Cystic Fibrosis Foundation this is him running in a event for the Cystic Fibrosis Foundation other people that are just tremendously inspiring like Kathy and Joe O'Donnell who lost their son to cystic fibrosis began to invest in development of a new medicine with the Cystic Fibrosis Foundation who then linked up with the company called vertex and in February of 2012 vertex announced that they had FDA approval for this new medicine it happens to treat the exact mutation that will has two weeks ago from today today will took his first dose of this medicine something we couldn't have imagined would occur when when will was born or over the last several years I talked to his parents last week and they told me that for the first time in two years he is losing a call that he has had chronically and some respiratory problems so after two weeks on this medicine a huge impact on his life so this is a daunting challenge I wake up every day feeling daunted by it but what I will say is that we can all be involved at some level whether running it for in something like great strides or doing anything in our sphere of influence to have an impact and it is not insurmountable but we all have to be serious about tackling these real problems to get to where we want to be thank you very much

Channel: TEDx Talks

Views: 18,211

Keywords: TEDxNashville, English, technology, tedx, health, ted, USA, ted x, education, ted talk, science, medicine, ted talks, tedx talk, tedx talks

Id: Lx27gzXLDic

Length: 19min 47sec (1187 seconds)

Published: Thu Apr 26 2012