Tomorrow's Breakthroughs Today: Dr. Steven Arnold

want to welcome everybody to the latest in our series of tomorrow's breakthroughs today for those of you that do not know I am Mark reuth Mayer I have the privilege and honor of serving as the CEO of the Alzheimer's drug Discovery Foundation this is the second in our Series this year and this is the second year of us running the series tomorrow's breakthroughs today let me start with a huge thank you to Heidi McWilliams who this was her vision over three years ago and she got Leonard and Ronald and Howard and myself to say this is a brilliant idea and look at this two years in so Heidi foreign she is with her significant other and the vice chairman of our board Tom McWilliams so Heidi and Tom it is always a pleasure to be here with you thank you very much [Applause] um Heidi is also the co-chair of Our Hope on the horizons Gala and where is Nancy Goods who's our other co-chair founder of the event and co-chair in the back and many of you know Nancy and we all love Nancy and also he's a wonderful Board of governor for us for those who don't know the event this year is March 15th we are honoring the one and only Bonnie Lautenberg and to say it is a hot ticket last year I think the event sold out in about the middle of February and we're on Pace this year we may be selling out by the end of January so if you're interested in not in yet it's a hot ticket so it's there other members of the family that are here with us tonight Ted Smith who's with our Board of Governors sitting up front Ted thank you for being here and we also have Let's see we have a couple of people Sharon Sager with her wonderful husband Laureen is here with us today Dave Gerson with his wonderful significant other Luis is here with us today and um oh and one of our newest Board of overseers bow I know you hear about Bal Agarwal is here with us tonight so it's nice to have the family of addf sports out with us tonight and for any of you that missed it The Other Board member that's here with us tonight the recently married with his bride Larry leads and ginger here sitting in front with us tonight and talk about a hot ticket interview that went to the wedding reception which was a couple of weekends ago which is just fabulous at club club Colette right yeah no thank you Larry um interesting tomorrow's breakthroughs today I can absolutely tell you that today the information you're going to hear is delivering on that theme many of you may have heard in the last couple of months and even in the last week about some breakthroughs that are starting to happening with Alzheimer's drugs breakthroughs from companies like Biogen acai and just last week some some new information breaking from Eli Lilly it's confusing when we hear about it it's confusing and how effective are these drugs who pays for these drugs when are these drugs going to get approved I can promise you all that's going to get cleared up tonight and you're going to hear about those drugs but you're going to also hear better because again the theme is tomorrow's breakthroughs today and you're going to hear about the drugs that I just talked about are these amyloid clearing drugs but you're also going to hear about Diagnostics and biomarkers that are unlocking the next generation of Therapeutics because the answer to this and anybody who's been to our series before the answer to this is ultimately combined therapies and precision medicine in five to ten years from now we believe that's in our sights and I'm not going to steal any more Thunder from the presentation tonight but what I will describe to you recently the esteemed Dr Howard Phillip and myself were out at the JPMorgan Healthcare conference in San Francisco where all the big farmers were presenting and one of the presentations was about one of the drugs I just mentioned and the CEO of the company got the question well tell me at 27 Effectiveness what does that really mean and the CEO answered well that means you could be driving a car for another year okay so that makes sense driving cover but what you're going to hear about tonight is taking us from 27 effective how close can we get to a hundred percent so it's just not about driving your car for another year but it's about remembering your grandchildren's name and never forgetting your children's face and again tomorrow's breakthroughs today you're going to hear about that tonight all right so to get us started I'm going to introduce Dr Howard Phillip 25 years ago not quite that Harry I'm coming 25 years ago uh Estee Lauder went to her two sons and said do something about Alzheimer's and as Leonard pointed out to me it wasn't do anything about Alzheimer's it was do something to be effective because this was a big family issue for the waters and what that turned into 25 years ago is that the Alzheimer's drug Discovery Foundation would only focus on translational science how do you take a good idea in a lab and get it to a patient to be an effective treatment and that the Alzheimer's drug Discovery Foundation wouldn't give out grants but rather it would make investments into biotechs into academics so that if they saw a return addf gets a part of that return and plows it right back into the science and then the other thing that the Lauder family decided was that with este's trust they were going to cover the costs of the entire foundation so that Harry and I could stand up here and say to all of our donors tonight every penny every penny you give goes directly to these these investments in the science okay and this concept of going bench to bedside you're going to hear about three different things tonight you're going to hear about prevention you're going to hear about biomarkers and you can hear about treatment and that was decided 25 years ago and the organization has been true to the mission so now I give you Dr Howard Philip he is a physician he is a scientist what does that really mean okay beside these two guys are there any scientists in the room oh okay well most everybody else I can get away with it sometimes scientists are considered nerds you know kind of nerdy right well physician scientists are really the cool nerds because they want to study the science you want to see how they can make people better with the science not just science for science sake but make people better Dr Howard Philadelphia is a physician scientist 40 plus years of having a true north only about how can you make his patients better he's working Academia industry and Now philanthropy to get a laser-like focus on that Dr Howard Phillip [Applause] a brief in introducing this uh I think Mark mentioned a couple of things that we're going to talk about tonight this really is an exciting year because really for the first time in history we have a drug approved for Alzheimer's disease that's a disease modifying agent to slow it down and we have two other drugs that are coming down the pipeline that may get an approval in the coming months so we will have three of these and Dr Arnold and I'll talk a little bit about that but in addition another interesting fact is that about five or six years ago the pipeline for Alzheimer's was primarily and these anti-amyloid drugs and amyloid is a protein specific kind of protein that's found in the plaques that are seen in the brain at pathology at autopsy and were discovered the plaques were discovered by Dr Alzheimer's when he did an autopsy on his patient who was a 52 year old woman who was demented he also sought Tangles which are the characteristic feature another characteristic feature of Alzheimer's disease and represents the dying neurons and in those Tangles this these discoveries of the proteins were made in the 1980s so almost 40 years ago in the in the uh in the tangles the protein was discovered called Tau which is a structural molecule in the neurons that helps to create synapses and the long connections and when it misfolds it kills the brain cells so the two earliest approaches going back to the 1980s to develop drugs for Alzheimer's really started from the pathology I think the advancement today is that we're moving towards understanding the biology of Alzheimer's disease and the pathways that get us to neuronal degeneration and dementia which Alzheimer's is the most common cause of dementia and our strategy from the beginning was really 25 years ago to look at these other Pathways that go beyond amyloid and Tau the typical pathological Hallmarks of the disease and really translate What's called the biology of Aging because Alzheimer's in many ways shares similar mechanisms to heart disease and cancer and and chronic lung disease and so on renal disease in that for example inflammation is a Hallmark of Alzheimer's disease and it's a Hallmark of aging and other things like vascular disease there's a Hallmark of aging and also very prevalent in Alzheimer's disease so what happened was about six seven years ago the worldwide portfolio was mostly about as a harvest of the 30 40 years of work was mostly about beta amyloid and Tau and you're seeing those drugs being in late stage development now but we're also seeing that the portfolio changed from 75 percent of the drugs and development being amyloid in Tau to now 75 percent of the drugs being directed towards biology that results in Alzheimer's disease and so we're seeing a lot of interest in inflammation companies like Denali and elector which are publicly traded companies are very much in the pipeline in phase two with anti-inflammatories very specific anti-inflammatories for Alzheimer's disease and um and and many other drugs then so there's about 120 drugs in development now as I say about 75 percent of them are novel Innovative drugs on on new Pathways and I'm proud to say that atdf has contributed in one way or another to about 20 percent of the drugs that are currently in clinical development the last thing I'll say Mark mentioned something about this that we'll talk about with Dr Arnold is that just like in cancer the way Dr Farber tried to develop cancer drugs he took cancer he took toxins and he gave it to people back in the 40s and early 50s and saw which of those toxins actually made the tumors shrunk on x and he realized that one drug wasn't going to make it because the cancer cell has so many abnormalities in it and so he added another drug and now he was treating cancer cells and cancer patients with two drugs and then three and four and so it took like three four drugs that's why people are on combination therapy today in the modern era of cancer you get your cells type you get a biopsy of the cell if it's a lung tumor and the Pathologists and the other doctors that are developed the biomarker will type yourselves and then tailor your drug treatment to your cells based on your biomarkers and that's been quite successful in resulting in The Chronic management of cancer and that's where we're going with Alzheimer's disease today we have biomarkers adtf has a 100 million dollar program to develop new biomarkers and the reason for that is because it's critical for drug development and I'm proud to say I'll tell One More Story Stephen and turn it over to you um is that um well I'll tell the story about how it happened in 1999 I was sitting at my desk and was pretty much the sole employee of the foundation and got a phone call from somebody named Hank Kong at the University of Pennsylvania who said that he wanted to develop a test a diagnostic test for Alzheimer's and of course we didn't have any the only way you could really get a living diagnosis was through a brain biopsy and that wasn't widely done but he wanted to take the same dye that Alzheimer used in 1906 to describe the disease and he wanted to radio label it with a fluorine atom that would make it possible to see that that die on on a pet scan on a typical pet scan that we all get he would inject it it would go into the brain if there were plaques in the brain it would turn up as a signal on the Pet Scan he said he couldn't get any money for it so we took risk on it we funded it for four years at Penn in 2005 the intellectual property that had resulted from that work was a spin-out called Avid radio for Pharmaceuticals with seven million dollars in Venture Capital five five years later in 2010 that company was bought by Eli Lilly for 800 million dollars in Milestone payments in 2012 it became the first FDA approved diagnostic test for Alzheimer's disease so in our practices if we want to diagnose Alzheimer's with some certainty we can send people down to the radiology office down the street and get this pet scan and within 24 hours have a high degree of certainty whether someone has Alzheimer's but the question is Lily's not in the Diagnostics business they're in the clinical trials business why did they buy it for 800 million dollars well they've got a program now where everyone maybe I'll turn this over to you Steve because you were involved in the Lilly program and the the um Johnson and Johnson antibodies and the Biogen um but basically that biomarker long story short was used in the clinical trials has been the primary type of diagnostic test used in the clinical trial to enroll patients to make sure that people in these trials with the anti-amyloid antibodies have amyloid in their brain that they have Alzheimer's and then using that test to show that the drug actually works to remove amyloid from the brain and now for the first time although you've heard a lot of controversy for the first time we can say whether the amyloid hypothesis is right or not that if you remove amyloid from the brain do you get a clinical effect and at least in my opinion I think with the three main drugs that have been tested two of them probably going to be coming to the FDA in the coming months within with I have a hopeful and approval we can show that the drugs work they remove the amyloid from the brain and that seems to be associated with a clinical benefit the first Biogen drug that was approved recently was approved on the basis of the tests that we started funding in 1999 because the FDA decided that there was a reasonable degree of certainty that if the drug removed the amyloid from the brain that there would be clinical benefits so that's a 25-year story but it tells the story of how drugs were developed and also how biomarkers play a critical role in the development of drugs I know Steve I'm sorry to steal some Thunder there if I did but I know you were very involved in in the clinical trials of the beta amyloid antibodies as a starting point and we talked about whether you might give us some insights into the clinical effects of the drug and whether if it came if these drugs come do come to Market and have patient access whether you would prescribe them for people in your practice and whether you think the drugs are worth it in terms of clinical meaningfulness and that sort of thing yeah so thank you Howard so that is a um that's a there's a lot to cover in this in topic and actually I was you know I had been at before I was at Mass General I was at University of Pennsylvania for a number of years and actually working with Hancock what's that I forgot to introduce you okay so but let me just say that um Steve's an old friend and he's professor of Neurology at Harvard and he's a managing director of the translational brain Center at Mass General Hospital and a clinical trials which we'll get to in a minute okay thank you um so um no so I was just saying that you know I was actually there at Penn with Hong Kong and Dan gabronski and and you know the others that really um were able to to take this amyloid Imaging um and turn it into something that we could scale up to really use in the clinical trials um it you know I it's hard to underestimate uh it's it it's hard to to kind of over over say how important how transformative the biomarker is that addf has been driving for for years now has been for the field and I think it's finally now really bearing bearing fruit you know as Howard mentioned we Define Alzheimer's Disease by these amyloid plaques and these Tau Tangles that we see in the brain and the Big Challenge really was if we're going to give it if that's if that's what's underlying the disease how do we actually measure whether a new drug or a new treatment can change it we need the biomarkers like the amyloid Imaging or you know spinal fluid or now we're moving into blood tests for amyloid and Tau so it's really a a very interesting time uh transformative time for us from the from the biomarkers but to get back to the the point of these anti-amyloid Therapies it's complicated um you know I think where and as I've been saying that you know these new drugs that we're hearing about um are a huge huge advance for science and maybe not such an advance for clinical care um meaning that you know Alzheimer's described these plaques in 1905 1985 we found out that the the plaques Were Made of This amyloid protein which is a normal protein we all have it's just an Alzheimer's disease the protein gets kind of crumpled up in the cells or between the cells and causes you know the the brain connections to to start dying um and so you know 1985 we discover amyloid you know how many trials I mean you were there you know how many trials billions of dollars spent chasing amyloid nothing worked in fact some of the drugs made actually people worse um and um and then now so you know I was really losing heart that why are we chasing amyloid it doesn't really do much um you know so I I say that it was a big scientific Advance now because these drugs finally are very effective at lowering the amyloid in the brain almost to normal levels if not normal levels and they do change the course of Alzheimer's disease but why it's not a huge clinical Advance is because they don't change the course of Alzheimer's disease that much so um you know so so you're taking the medicine even though your amyloid level is going down to almost normal levels the disease is still progressing it's still getting worse not as fast but it's still it's still getting worse and to me that says okay amyloid is a factor in Alzheimer's disease but Alzheimer's disease is more than amyloid something else is driving it and whether it's the Tau Tangles or whether it's the inflammation or the metabolic problems or vascular contributions those are the you know we you know so I I almost view that you know okay we've got amyloid we can get rid of amyloid but it's not enough what are the other factors that are that are driving it um and so that's you know part of the work that we're doing we are running um you know what Johnson Johnson has an anti-tau trials in the same way that these antibodies these immune therapies for amyloid well there are immune therapies for Tangles I'm not so sure they're going to work I I don't know um uh there's a gene therapy that's about to launch that kind of cuts underneath the gene that makes Tau maybe that will show some signal but I really do think that the answer that that aside from cleaning up amyloid and Tau as Howard mentioned you know we need to go after some of these other things like inflammation like vascular like metabolic dysfunction um uh in in the brain so you've been involved in some other things that adtf has funded one of the things you've been involved in was probably the first combination therapy clinical trial in the history of the world which was a company a very interesting company that lets you tell the story of about called amylix which is now publicly traded and has a drug for ALS on the on the market I believe yep and yeah and also obviously we we invested in mlx very early on to do a combination therapy so as I was saying earlier combination therapy will probably be the gold standard for the treatment of Alzheimer's down the road but we haven't started doing the combination therapy clinical trials yet because we don't have the individual drugs to to put into these combinations we need to show stroke kind of works before we can combine them but that's not the way cancer actually evolved you know Dr Farber was just going out there and throwing drugs at people and an amaleks in a way had a theoretical basis for using sodium phenylbutyrate and torso dial I think it is something like that I always get the name wrong but uh yeah but since you were involved and we invested in it I'll let you tell a story yeah it's a really interesting story and it's actually one of the the joys that I've had since I've been up in Boston is kind of working with all these you know small biotechs that have just unbelievably creative ideas about you know how to how to approach things but you know as as I was saying you know as creative as they are that's how ignorant they are about what real patients are like and what the clinical translation is like so this is a really interesting story these two two young kids literally you know in their mid-20s graduate from Brown had this idea that if you combine these two old drugs together you could get some synergistic effect to deep to protect brain cells so there's this drug called sodium phenylbutyrate which has been used for you know a metabolic disorder for for years there was this other torso um they they call it now which is uh actually related to it's actually a derivative of a bare bile of all things you know almost a Chinese traditional medicine that's used for gallstones and and things like that and they put they based on what they I guess study lead in undergrad you know put these two together tried it out in a little culture dish of cells that were exposed to hydrogen peroxide you know something that stresses the cells and the strel and the cells lived so then they come to us at Mass General and they spoke with me for Alzheimer's disease with Merit sudkovic our chair who does work in Lou Gehrig's disease ALS and they were able to get some funding from the ALS Foundation a year later we were able to pull together with with Howard's help in addf some funding to do a combination trial in Alzheimer's disease well the ALS trial got a first and you know unbelievably lucky it slowed the progression of ALS down by a good amount and ALS is a rare disease it's easier to get approval for for drug you know drug approval um the FDA approved it so you've got this tiny company that was like you know three people when when it started um now you know with an approved drug that slows down ALS and then with the the addf supported trial that we did in Alzheimer's disease the results just came in last last about a year ago you know the Top Line results the trial was too small and too too um short you know in six months we didn't see any Improvement in memory or things but the biomarkers we found it drove downtown it drove down thought you know something you know a different kinds of Tau it improved amyloid um it decreased oxidative stress and so here now we've got you know a novel idea two old drugs combine them together they protect the brain they drive down Tau it's a signal and it's something that we can now and the company now is going to pursue to see how good it can get with with Alzheimer's disease and I think the the story Steve is telling here is is a story of human clinical research because this is a disease that's a disease that is uniquely human it's the lawsuit sorry thank you is the loss of the human mind um and and you know though we've cured mice about literally 700 times without various forms of Alzheimer's disease the translation of those studies into human beings has been difficult if not not very successful and so I think so one of the things that Steve and I share here is that is clinical research I trained at the Rockefeller University where clinical research actually led to the discovery of DNA um and I worked in that Laboratory um so that DNA was the genetic material of life I should say um so you know I think this idea that we need to get more efficient at getting drugs into human beings and doing studies of how these drugs work in human beings even if they're not the most successful we learn from every single clinical trial that we do and we can build on that and I think that's what we've been doing over the last 20 30 years is building because I one of the things that I think we've talked about here but I want to emphasize is that when I ran one of the first clinical trials it was a very small trial back at Rockefeller in 1981-82 I probably would be fair to say I had no idea what I was doing um you know I gave somebody some women oral estrogen at the time for good reason and it's kind of coming around again but um but now we're so precise we have these biomarkers we can identify patients we can use the biomarkers to see if the drug is working or not I mean it's a very different year I think we're in a very different era of clinical research we can ask very precise and careful questions of how these drugs work in human beings and learn from it and build on that so it's a it's an exciting time in the field you were also well the the amalek story is a story of repurposing essentially and that's something that we're also interested in is in in repurposing drugs we've run about 19 clinical trials of repurposed drugs we've had some success they've been published in the medical literature and the foundation is very much interested in having commercial strategies such as developing novel intellectual property so that we can try to bring these repair purpose drugs to Market and to give an illustration of what repurposing is in terms of success and so on thalidomide was a horrible drug for pregnant women back in the 1950s someone had the idea in a couple of decades later that thalidomide might be good for multiple myeloma and so they tested it in patients and sure enough it worked really well started a biotech company called cell Gene which became one of the most successful biotechs in history an example of repurposing an existing drug where the safety profile is known and where the drug is already on the market it's known to the FDA and then testing that drug in patients with Alzheimer's disease for good reason and when there's good reason and I guess one example that we were talking about that we've also helped you with isn't is an antiviral drug that's used for HIV AIDS and maybe you could tell us that story yeah so that's that's another interesting story so there's a a drug that's used for HIV it's called sustiva and usually it's used at very high dose for for AIDS and HIV you know 600 milligrams but a researcher that we collaborated with over at Case Western in Cleveland you know was screening drugs that changed cholesterol metabolism in the in the brain and notice that at very tiny doses you know maybe five milligrams not 600 milligrams five milligrams that it turned on an enzyme that improved the cholesterol turnover in the brain and with that um you know we went to addf with this idea that you know we know that cholesterol is really important for you know for for many things um but you know it's almost like the brain is not able to kind of turn oh in Alzheimer's disease the brain has trouble turning over cholesterol um so here we have a a drug that and a tiny tiny dose seems to turn on that that turnover and you know we we went to addf and they they funded a small trial and you know we um you know we were able to to develop some new biomarkers that can look at cholesterol turnover in the brain through a blood test um and you know I think the we're still wanting to we're you know we're not there yet we don't know how effective it's going to be um but it is it's a it's another example of how addf kind of takes risks and to drive the field forward with novel ideas wherever they come from whether it's from you know a company that has a new compound or you know an old drug that can be repurposed because as I like to to say you know we it Howard was was mentioned the difference between you know basic science research and clinical research and you know as I you know we've got if you're a mouse it's a great time to have Alzheimer's disease we can cure you you know we can absolutely cure you we've got hundreds of drugs that work in mice um but people are not mice and sometimes the basic scientists don't quite understand I'd like to say my stone right books um and um you know and and so like one of my really tremendous frustrations has been the way you know that that the way drug companies or other places actually try to develop drugs is as if people were mice and you know that so just the way that you design clinical trials now you're pretending that everyone is the same and you put one one Mouse on the placebo and one Mouse who are a genetically identical environmentally identical and you put one and then you compare them well that works great in mice but people are different you know there's white people black people brown people fat people skinny people you know people with arthritis people with high blood pressure people everyone's different um and we pretend that they're all the same and so this is you know part of our drive you know again using the biomarkers that that um some of the that addf has helped develop and and all can we actually profile individuals and can we actually personalize clinical trials and I think that that's that's the future and we're we're interested we're really interested in this personalized approach uh what we call n of one studies in other words instead of as you were describing the way we do it now is 3 000 patients enrolled in 300 different sites around the world in 20 different countries 1500 get the placebo 1500 get the drug and then you do all the statistics to see if the drug works all for the low low cost of a billion dollars right and that's that's right it's a billion dollars and you you have a new way of looking at this which we're very interested in which is this ability to test one patient at a time through your seed program which I forget what that acronym stands for um and then maybe create a platform where we could help you to to study drugs and individual human beings and see how the drugs work in those patients with Alzheimer's disease gain information maybe aggregate the data after these multiple and of one studies and then maybe the signal if it's gonna if this uh if there's enough of a signal there then take that drug into a regulatory pathway so that there can be Market inpatient access so maybe you could just tell us a little bit more yeah so you know I really think that this is it is taking the cue from what oncology has been doing for years and we've never been able to to do that in Alzheimer's disease until recently when we do have these biomarkers you know whether it be a blood test a spinal fluid test an imaging test um you know now that we have these new tools it's a different it's a different game and we can Pro we can you know um you know like in breast cancer you you kind of do some genetic testing on the on the tissue and you know if someone's hair too you go into this you go into this drug or this drug combination if you're not here to you go into that combination well we feel like we're just about ready to do that in Alzheimer's disease where we can you know analyze someone's blood or analyze a sample of of spinal fluid or do some MRI tests and try to match up the right kind of drug with a person's particular unique biology which you know my Alzheimer's is different from your Alzheimer's disease I mean that's just we have different backgrounds we have different genetics we have different you know other medical conditions that that could be driving it so you know one of the thing is to match the right person to the right drug at the right time and then the other huge thing is the ability to actually say whether the drug worked or not and that's where some of the new blood-based biomarkers are coming up if we were able to measure someone's towel level in their blood for you know two or three times so that we know exactly where it is and then we put them on on a medicine and we take a few more blood tests over the next month does the towel level go down and then that's really the first step we've demonstrated that a new drug may actually change the biology of Alzheimer's disease and then you have to graduate I mean in order to get FDA approval you need to move it on but we can create a data package that can be helpful for advancing drug into the larger more definitive trials that the FDA might accept for for approval so that's how I think that the you know personalized medicine is finally starting to come of age in Alzheimer's and you're you're you've told me that you think this would be able enable us to do this kind of clinical research in humans for about one-tenth the cost I think you're estimating that's what our statisticians are are saying that if people serve as their own controls not that I'm comparing you to someone else from a different background who's in you know in different geography and and everything um that the the the the power what they call the statistical power of detecting real change Within individual is much greater so instead of doing an initial trial with 200 people or 300 people we think we can do it for with 10 20 30 people and get similar results and I know you want to set up a platform where we could even test different drugs so if we if we characterize one patient as having amyloid and Tau plus inflammation they would go into one bucket maybe the next person at samyloid and Tau because those are criteria for Alzheimer's plus some metabolic disorder and they would get another drug and that's that's our vision also at addf that the biology of Aging is very complicated and we need these buckets of treatment ultimately to to to as you said your your Alzheimer's is different from mine or I hope neither one of us haven't actually um you know another another drug that we spoke about is that you're also testing is uh nicotinamide riboside which there's a lot of interest in that and it's precursor that we're also investing in through a company holding company called Eden Rock um but maybe you could tell us that's a that's so that approaches the pathway of of the metabolic disorders and mitochondrial problems in Alzheimer's and in aging and maybe you could tell so they're you know there are these things called nicotinamide riboside or there's also nmn nicotinamide mononucleotide um these are related to certain b v you know vitamin B certain B vitamins um and what they do is they kind of boost the energy producing capabilities of brain cells and we know that in Alzheimer's disease you know that the metabolic energy um starts to decrease for lots of reasons amyloid partially but many other reasons so the idea is that this you know this the the this nicotinomide riboside or nmn boosts these NAD levels to improve the Energy Efficiency of brain cells and you know this is we need to test whether this is going to work this is one of those examples you know we talk about drugs but you know there are also natural compounds supplement dietary supplements that as you know look every bit as good as some drugs in the dish or in a mouse do they work in into into into humans how do we put them how do we design a clinical trial where we can actually um you know see whether it works and I think that that's you know that's an example of you know we just completed a study I don't have the results yet um uh uh you know there are a few other studies addf has been interested in this you know it's hot it's a hot area we need to know whether there's actually a there there um and that's what these trials are so so we are interested in supplements that are exciting and we have a website called cognitivevitality.org where we have three neuroscientists working full-time to do analyzes of supplements and other drugs and vitamins and so on to see whether there's evidence and whether there's enough evidence to start studying these like NAD and on the energy side that Steve was talking about the brain is about two or three percent of the body weight but at any given moment it's using 25 percent of the energy that we consume through glucose or through oxygen so this pathway is critically important if you think about it a diabetic and diabetes is a risk factor by the way for Alzheimer's and there are drugs that are being re there are diabetes drugs that are being repurposed for Alzheimer's now for the same kind of pathway reason about alternate metabolism with aging insulin resistance and these these brain cells are the most active cells in our bodies and they're so dependent on energy if you think about it when a diabetic takes too much insulin what's the first thing that happens almost immediately when their blood glucose drops below about 60 or 45 or something like that the first thing that happens is people go unconscious that's how dependent the brain is on glucose for energy and so imagine like you're just kind of using your energy inefficiently over time on a chronic basis your brain cells are going to be at risk and the the other example of this NAD is that we are testing supplements because we think it is part of our job as a foundation as a non-profit to see you know I get so many patients come into my office I once had the ambassador to France come into my office with his wife and um you know I took a history he was suffering from early mild cognitive impairment and I always ask my patients to bring in all their drugs in a in a bag well she brought in the bag and we lined up all the drugs and he was on about 30 different supplements and you know a lot of these supplements don't get analyzed we don't know what's really in them they argue they advertise it to ashwagandha and it's going to be good for your brain health we don't know how much ashwagandha is in there and we don't know if there's arsenic in there also unless they have the USP label on the front of the vitamin or the supplement that has been analyzed by this disorganization so anyway we put it on put it all out there and I started going through them one one by one I said you can get the report on cognitive Vitality this doesn't work there's no evidence she said all right throw it in the garbage I threw that one in the garbage next one back in the garbage and the guy walked out with about five out of 30. and about a couple of weeks later his wife called me up and said I want to see you and I thought maybe I missed something in the history that she wanted to tell me you know by it by herself when she came to see me and she came in with a roller bag and I figured she was the ambassador's wife and she's on her way to the airport and she says no I got all my drugs in the roller bag and I want you to go through them and you know it's a some team multi-billion dollar industry that people are taking these supplements and we don't really know their value or whether they work and some of them could really be tremendously of value I think Nat is is a good example but it may we know NAD is not the right precursor the riboside but the nmn might be anyway we don't know that yet but but that's what we're testing so that that's another example of kind of how addf works please and donation we couldn't bring the salt itself up and there's actually my nurse came up with the idea of that and you said Mrs Travers have you tried salaries we have been giving my husband Jews for over many many years four or five years every day so I increased the amount of celery in the juice to like 12 inches two of them and it brought the level of the salt up six points to a to a situation where the hospital could discard discharge us and we went home it has been since July the level of salt came up initially but I have three nurses that handle the day situation and when they were inconsistent it went down again to 28 so we now put it you know measurement on it and to make a long story short the soft level is now completely came up to normal at 1 35. the most important thing that this did was his draw somehow it has balanced his body to a point where the medication the levodopa for Parkinson has dropped in half his yo-yo blood pressure went from every two hours to every four hours so now we only need the medication for Parkinson half as much so something like that that's most effective I thought that nobody would be interested in looking at it because there's no way that drug companies can make money on encouraging people to go buy celery juice but I would like to ask you a question would addf be interested in looking at the natural food substance and their effect because I also had stye in three eyes and couldn't get it to come down with a dose of antibiotic and boiling parsley took it away overnight well I mean you raise uh I can't comment specifically on celery or parsley but I think you raise an issue which we said we would talk about which is prevention and you know among the 10 or 12 items of prevention that we know about sleep don't drink alcohol don't smoke cigarettes exercise manage your diabetes and your hypertension and your hearing loss and your vision loss and I've probably forgotten a few sleep I think I mentioned and if you if people did all the good things that have been recommended we can reduce the the the incidence of Alzheimer's probably by about 40 percent and there was a randomized trial called the finger one of our board members conducted it in Finland originally and now this study is being replicated in 45 countries around the world and this study showed that with with proper with all with an intervention that ensured that people were compliant with all of these activities that they had to do that you could slow down the disease and prevent you know the progression of memory loss let's say with aging um and a very important component of that was the Mediterranean diet and you know eating a lot of vegetables grains fruits and and so on and maybe it's because those foods have a lot of antioxidants or other factors that we don't really know about so I think diet is recognized as as one of the specific preventative measures the same way it is for heart disease it's good for your brain so I think food in general uh you know commenting on individual Foods we would have to do a report for you on celery on the cognitive Vitality website and get back to you on that one I don't know if we're ready for questions or not but um I I think so um I think we've covered most I mean there was one other thing we talked about Stephen that was um and I we might get questions on it and that was the Cognito program in Boston and sort of the the electrical stimulation we talked about the the alternate current and the direct current electoral stimulation and the light and sound devices and you know these people crazy or they um is this really going to work and it's you know there's a big industry growing now with these devices so I just wondered so you know the the whole field of neurostimulation um is is a burgeoning field right now and there are different ways so this you know we aside from you know nutrients and vitamins and drugs and and things like that to to change the brain chemically um there are different techniques to um that are used to kind of electrically stimulate the brain or magnetically stimulate the brain or and there's a lot of interest in this and that you know by so so one of the things um that Howard was mentioning mentioning um you know Cognito is a is a company that you know if you stimulate you know you wear this this headgear you know for both your ears and your eyes and it flashes light and sound at 40 Hertz 40 times a second um and that is a um you know a frequency that can help and train brain waves in a supposedly in a healthy way I'm not sure I'm not I'm not sold yet but the studies need to be done because it is important there are other things there are other things that you know something called transcranial alternating current um stimulation or transcranial direct current stimulation again you know stimulating with electricity or magnetic waves at a certain frequency to sort of entrain the brain into these kind of healthy rhythms I think that there's something there we don't they haven't been you know with the the research is going on um the other thing that we we think about sometimes is that can buy it may actually be a critical thing to combine a medicine or a nutrient with the the the stimulation um the medicine can kind of change and make the brain more malleable to this kind of healthy stimulation or or entrainment again that's something that we can you know we can do um yeah so um I'll just conclude and go to questions so we we have funded we have invested in this company called Cognito which was spun out of MIT and we also funded a clinical trial in brescia uh in Italy of a uh of the transcranial electrical stimulation and it seemed to work I mean quite frankly it seemed to work um but but I think you're right we need to do the research these things are on the market people are buying all kinds of helmets that do stimulation and stuff but the way I kind of got to it is when when we want to analyze the brain we often do quantitative we do EEG and now we do quantitative EEG which is telling us something about the electrical signals in the brain that's related to disease and maybe there's some way that this stimulation is normalizing that signaling because like you said it's in training means that it's kind of coordinating all the centers that need to be coordinated in some way so they're all in the same wavelength somehow that's a brain function the brain is an electrical organ as much as it is a chemical so it's it's kind of interesting it's at the Forefront yeah we're doing good Tech questions yeah yes sir again thank you for the wonderful presentation my question I'm just curious about melatonin that's produced by the pineal gland in the brain and most people who develop cognitive decline always complained about Sleep disorders and melatonin of course is produced by the pineal gland and helps us sleep at night and particularly in the Deep stages of sleep and the REM stages of sleep so as as said men in any basic research done on melatonin and epineal gland and the second quick question is what role does artificial intelligence going to play in solving this riddle those are great questions um I'm pretty sure we have a report on cognitive fatality about melatonin something I've read recently is that a lot of people oh this is our founder but I better tell him going back I'm on stage now with the beach okay thank you um well whoops I'm sorry so um so yeah people take melatonin for Sleep um and there there has been a lot of research on melatonin and there was there was a company back away so I remember like maybe 15 20 years ago that did some studies to see if melatonin actually reduced amyloid in the brain and this kind of thing I think if you're taking melatonin for sleep it's worth just trying it and seeing if it works for you basically and what I read recently is taking maybe three milligrams is better than taking the 10 for whatever reason the lower dose seems more effective but there is a lot of research and so you could go to the website Supply and have lower melts I don't think we know if they have lower it's not it's actually yeah it's actually not that the Melatonin is is a sleep inducer uh for some people I'm not aware that melatonin levels are actually lower I think you know clinically it's usually where I start I it usually doesn't work um I'll I'll have to admit but it's usually I I ask I suggest to people start with melatonin if they are having a sleep problem start with melatonin if not there may be other things but the point that you're bringing up is how important sleep is and especially the deeper stages of sleep for clearing the metabolic waste of the brain including amyloid and when we get you know there's this whole lot of interest in something called the glymphatic system which is basically um you know a way to that in deeper stages of sleep a lot of this you know metabolic waste metabolites you know get washed out um and you know one of the theories is that in people that have sleep difficulties for whatever reason that they never you know like sleep apnea they never get down into the deeper layers levels of sleep where they can cleanse their brain um and it's it's a very very fascinating area of research and Sleep Disorders are really common among people with Alzheimer's disease and that can be very debilitating and they can be very debilitating and um what I often see is people you know 80 85 years old with cognitive impairment coming in and they're on Ambien or they're on any of the sleep and I know when I take it if I do it gives me a terrible hangover and I I just find it really causes memory and I so I almost uniformly asked people to get off those drugs that are prescribed and very often people feel better when they're off the drugs even if they're not sleeping fully through the night but sleep disorders are a big problem and there's some new drugs on the market now that have new mechanisms that might be better than the drugs like Ambien and Sonata and drugs like that yes I have a a question statement question which is it's been a long time since people have discussed whether amyloid causes Alzheimer's or whether it's a symptom and I guess you've touched on it but are you we any closer to figuring that out and then I wanted to ask you about all the brain games people do thinking it's going to hold off the inevitable crossword puzzle Sudoku uh do you want me to I can I can pour it all yeah Scrabble um so so the the the amyloid question is not nothing's simple or straightforward in Alzheimer's disease there are some you know amyloid in itself can cause the full spectrum of Alzheimer's disease and we know that in people that have you know these mutations in the pre-senaline gene or the eight you know amyloid precursor protein that it amyloid is the first thing that happens and then they develop the full picture but that's rare and most people with Alzheimer's disease while they have amyloid it may be due to other things influence you know immune problems or or we don't know yet you know metabolic or things that make it worse so it's it's complicated it's complicated um the so that that's that that's that's one thing um there it depends I mean there are some genetics that are very strong and there are genetics that are moderately strong and then there are genetics that week so we all have you know lots of genes um you know if you have a mute if you have you know the apoe gene many people have heard of that the April lipoprotein e Gene um you know and if you have the type four one copy of the type four your risk of developing Alzheimer's disease is higher but not hugely higher than the general population if you happen to have two copies because we all inherit one gene from our mother one gene from our father if you happen to have two copies then your risk is about tenfold higher than the general population again but I you know I've you know in in my research studies you know I've seen people I've looked at brain tissue from people who were 95 years old two copies of the E4 Gene you know they died and they were sharp as attack to the end so even though you have the gene it's not a guarantee that it actually causes the disease and then there's other what we call genes of small effect little things that you know if you add them together they increase your risk three percent four percent I don't know what to do I'll just add to that um the disciple before interesting carries cholesterol and is involved in neuronal repair um about 20 of the population is what we call a carrier so they either have one or two copies of the of the apoe4 there's also an apoe two that's protective so if somebody has a two and a four they actually have a neutral risk so what we did we we try to fund a number of ways to drug this problem to figure out how to fix apoe4 because well 20 of the population has apoe for 60 percent of people with clinical dementia from Alzheimer's have apoe4 so when we've known this for almost 30 years and haven't been able to develop drugs so what we did we've been working with Dr Ron Crystal who's the chairman of genetics at Weill Cornell and is a geneticist who's developed genetic therapies for other diseases and what he did is he took the apoe gene put it into a viral vector and then is injecting that Viral Vector which is non-infectious into the brain of originally non-un primates and now FDA approved he's testing this apoe 2-4 Gene Vector in human beings and he's been able to show so far that the vector works that we can see apoe two protein in the spinal fluid of these people that are apoe44 and the next step will be that anti-proof safety in about 15 people with different dosages he'll be able to go to a phase two and see if it actually slows the progression of the disease incredibly exciting work you know that that group yeah it's a company called Lexia yes with the E.I Lilly study there they said about their drug Donna whatever it's a tornado map so what I'll take a crack at that um basically um what they what Lily did in that trial I think was very Innovative because what they had for the first time was what's called stopping rules so these drugs are really expensive and you know the way it's been kind of developed at this point people kind of would be on the drug for a very long time I mean the trials were 18 months and then you know presumably if it came to Market people would be on the drugs from who knows how long you know three four five years perhaps how but what Lily did was they said let's see what happens at six months and they had 60 percent of the population at six months had dropped their amyloid levels on that brain scan below what was essentially detectable and so those people at six months even though it was an 18-month trial those people were stopped the drugs stopped now the original protocol for the trial said that Lily would present a hundred people to the FDA that had been either on drug or had been exposed had been exposed to drug and were followed for at least one year but because of the stopping rules only 59 people actually got to one year so the FDA said you know everything was great about that study I mean I thought it was really impressive it you know we don't see studies like this in in our field and you know the drug hit on every clinical outcome almost every biomarker I mean it was really an impressive study and when they filed for what's called an accelerated approval which was based on the biomarker evidence the the FDA said yeah you know you got all that but we're worried about safety and you Pro you told us in the protocol that you'd bring 100 patients to um to safety at 12 months and you didn't do that so the FDA said let's go back get the 100 patients the the fact of the matter is the bottom line is it's not going to affect the development of the drug because the phase three studies are going to be available in a few months and at that time if those studies look good Lily will go directly for a full approval they won't go for that accelerated approval so it's it's kind of understandable there's some thought that maybe FDA changed the goal posts a little bit but I I think it was just really a safety issue that was a fair concern and I don't think it's going to change the development of the drug and I think the drug will probably get to Market I don't know if you have any other thoughts on that yeah no I mean I I love the design I think it was rational it you know it did what it it um you know they said that they were going to do um and it worked um you know I think the first priority of the FDA is safety so you know they want to see the number of people as many people treated with a drug in order to be assured that it's it's safe I happen to think it will turn out to be well so none of these three drugs the Biogen you know the edge of Canada map Biogen the cane map they all come with some Siri very serious side effects that we have to be you know worried about it's about 20 to even 40 percent of people can develop brain swelling hemorrhages and you know so you have to be you you have to go in to these these kind of treatments with your eyes wide open they're not you know um but um and that's also part of why I said this is a huge scientific advance but clinically you know I'm not it's going to take some work to to work with a patient to decide whether it's right for them or not acknowledging the risks that are involved yeah I mean we did a study um where we about five or six years ago we published it where we interviewed um a couple hundred people older people and asked them what kind of risk they'd be willing to take if there was a drug that could stop Alzheimer's disease in its tracks and one of the questions was would you be willing to risk death or a major stroke if you could take a drug that stopped Alzheimer's in its tracks and yet 40 percent of people said they were willing to risk that I think we all feel the back way you know we take cancer drugs that have horrible side effects and you know extend life you see it on the Nightly News there's that little white thing at the bottom that you can hardly read and it says you know this drug extended life expectancy by three or four months and everybody vomited and was nauseous and lost their hair it was disgusting and um you know but people wanted you know this is in advance in the in the field and I think for us in in the Alzheimer's field um I agree with Steve there's serious side effects but I think they're also manageable and the the number of people that ultimately have clinical serious clinical effects from that is is rather small like 20 might have area or 30 but the number of people that actually have serious side effects um is like five percent or something like that so I think people you know if they have if there's efficacy um and let's say you're 80 years old and as we mentioned I think Mark mentioned earlier you know if you got an extra year or two of recognizing your grandchildren would you be willing to take that risk and that's a discussion that would go between the doctor and the patient to decide yes thank you I have problems sleeping for a very long time and I don't take any sleeping pills because I'm told by my doctor that's the road to dementia obviously it is there is studies to show that people that take uh these anti-sleeping pills uh over time are at greater risk for dementia feel about cannabis do you have the same feeling about I know a lot of people who take cannabis before bed in the form of gummies or a puff and they have a good night's sleep yeah [Laughter] um it's legal now it's legal in New York yeah I guess I can talk about it um yeah I think cannabis is is um you know worth a try thank you yeah yeah what could you explain what that is and what the side effects are yeah I don't know that there's any side effects in in the process of uh changing glucose sugar into energy there's a whole biochemical pathway and NAD I think this is fair to say it's David correct me if I'm wrong um then in that biological pathway a critical sort of accelerator of or enabler of that conversion of glucose from food into energy that the body uses into basically phosphate is this NAD and generally you know you can buy NAD anywhere I would get it from a USP Pharmacy but generally what what I've learned is that the the body is usually not deficient in mad it's just not NAD it's just not able to use it the type of NAD that Steve was talking about is called nicotinamide NAD riboside which is a particular form of that but the nmn which is the I forget what that is mononucleotide that's a precursor to it so it's thought that if you have more of the precursor you can more I want to say organically it's not the right word but naturally kind of use your NAT because it nmn drives NAD did I get that right yeah yeah sure yeah yeah it's something like that but there's more I think there's good evidence that nmn might be more effective than the NAD but they're all in the same pathway any other questions all right well I want one more question last question going back to Emily plaque so maybe I'm wrong but the studies that I've read there are a number of people hundreds if not thousands who have no amyloid plaque on the brain whatsoever and yet they have Alzheimer's so the question is why is everything or the preponderance of research is predicated on you have to have online therefore it is Alzheimer's or it's a precursor I think there's there's a lot of confusion with the term Alzheimer's disease and the way I like to try to describe it is if you had plaques in your coronary arteries we would say that you had atherosclerosis coronary atherosclerosis as an example but you might not have had a heart attack and there are people that have heart attacks that don't necessarily even have coronary or atherosclerosis if you have a heart attack we would say we could say you had a myocardial infarction but you probably got that from the coronary atherosclerosis so what I'm saying in an analogy is that what I think a better nomenclature for describing a person what we call syndromally in other words describing the person in the clinic when they're alive is that they have Dementia or they have mild cognitive impairment which is a precursor to dementia so that describes the patient we use the term Alzheimer's disease interchangeably with dementia to describe the patient but the real I think the better way to um to to do this because if people have plaques and Tangles then pathologically it's like having plaques in your coronary artery they have Alzheimer's disease but it doesn't tell you what their clinical characters look like if they are demented and a better terminology would be to say someone had dementia from Alzheimer's disease because there's many different causes of dementia including vascular causes and other causes so if I can kind of not go too much around in circles here Alzheimer's diseases use both to describe someone who's demented when they might not have Alzheimer's disease unless they have the biomarkers positive but if they have a biomarkers positive then they have Alzheimer's disease they have pathology and that's a more certain way I think of using the term if you want to use the two together that's fine you can say dementia from Alzheimer's disease but I think to say to use the term interchangeably between the clinical description and the pathology causes confusion does that make sense no all right uh yeah I must be getting tired maybe I should turn it over to see if it's even closer soon I mean disease disease you know when we use the term disease it means there's pathology there's something that you can look at under a microscope and see when we use like a clinical syndrome or a clinical it means the symptoms and the signs of it and it's it's very actually very interesting that the you know while most people that have lots of Alzheimer's disease pathology meaning the plaques and the tangles in the brain most of them have Dementia or mild cotton impairment not all of them do and you know I was involved in a study for a number of years um called the religious order study these were about a thousand older nuns priests and brothers who were all kind of coming in for cognitive tests every year they all agreed to brain donation when they died and we looked at their brains afterwards and counted the number of plaques and Tangles and and such and about five to ten percent of them had lots of amyloid and tangles in their brain but they were normal in their memory and thinking and conversely we did find a small number percentage of people that we couldn't find any amyloid or Tau we couldn't find any vascular lesions we couldn't find any Parkinson's or Lewy Body Disease or any other cause and they had profound dementia so you know there's lots of ways in which the brain breaks down it's not just amyloid it's not just how there are multiple factors many of which we understand many of which we don't at this point so it's it's a fascinating question that you're you're raising so to conclude my daughter gave me a plaque that I have in my office that says if we knew what we were doing we wouldn't call it research and that was that was a quote from Albert that was a quote from Albert Einstein so I think we're in good company terrific first of all pretty cool docs right but I have two give me 30 more seconds I have two final questions and I think you want to hear the answers Richard what are you most excited about as you look at the field of Alzheimer's disease research right now um I actually think that it is it's as we've been talking the whole time you know we are moving beyond amyloid and Tau and we're capturing with biomarkers with our understanding of the disease the complexity of the disease so or the the complicate I have a colleague Brad Hyman who at our at Mass General and and um he says you know complicated is difficult complex this is where someone said about AI you know if something's complex we're never going to understand it we need to let the computers figure it out um but it's a complicated disease and I think we've been making tremendous Headway and I think that you know the whole move towards I think personalized medicine is where is what you know is is what we're going to do we're you know I don't Howard doesn't treat Alzheimer's I don't treat Alzheimer's we treat patients and each person is their own kind of entity so Howard picking right above that paint the picture it's five to ten years from now you have patients coming to see you what's the landscape look like what's hope look like Finance biomarkers we're invested in a company called quantarix that develops biomarkers and sells the tests through their machines and we just had a due diligence call with them to look at their progress from our investment and what they're developing is a blood test and we've already invested in the first blood test to come to Market it's on it's on the market for beta amyloid it's a blood test that correlates with the brain scan so this is not pie in the sky this is happening in 49 states except New York you can walk into a doctor's office and get a blood test now for Alzheimer's which is incredibly amazing but what we're starting to see is panels of different biomarkers and that's the one that we're invested in right now is is four different biomarkers and one of them is is a derivative of the of the brain um wires that fall apart with the disease and certain structural features that correlate with progression another is from the cells in the brain that are basically inflammatory and the another two are from amyloid and a fifth one that's in development is Tau so we've already got a panel of five different a panel that's going to come to Market I believe in the next year or two that that'll characterize patients along the way that we've been speaking and we'll begin to personalize their their disease in in clinical trials and I think that will lead to personalized medicine so the the immediate thing that will change is we're going to have these panels of biomarkers to characterize the disease the way Steve's been talking and then that'll enable us to do very careful clinical trials with combination therapy so maybe somebody will go on an anti-anyloid antibody and will add an anti-inflammatory I think that's what's going to happen next something like the ones that electoral Denali is developing um and so people will be on two or three different Medicaid locations and I think that will happen in the next five years and again you mentioned in the beginning we want to we want to if these anti-amyloids slow it down by 30 we want to get to forty percent fifty percent seventy percent and then we're going to have clinical significance it's going to be clinically meaningful and I think we'll get there in the next five years or so okay um cool scientists again right thank you very much doctors which is phenomenal um May 15th is um Our Hope on the horizons event we have a wonderful lecture that's going to go on there with Dr Philip and Dr Miranda Orr who is this past Year's Goods Prize winner as in nail and mancy Mel and Nancy Goods not Nell and Nancy Goods um and that is the prize that's given out to the top clinical scientists in the of the Year annual award worldwide and I want to come back to that last question because it's a great one and just paint this maybe at the 10 000 foot level you hear so much about amyloid because 10 years ago Pharma came in and said we like this remove the plaques and Tangles that'll be good the end of the problem and Dr Phil at that point went to the board and said we do not need to put any more science dollars into the amyloid Theory because Farmers come in and done it and that's what we're here for fund the valley of death so that farmer will take it across the Finish Line because of the Diagnostics that have been developed through seed funding and ongoing funding from the Alzheimer's drug Discovery Foundation those amyloid drugs are now down to pegging them maybe it's 30 percent maybe it's 27 percent that will be helped by that and Dr Phil it has led a 10-year charge into the pathways of Aging that cause dementia and that may lead to full-blown Alzheimer's but may only lead to mild cognitive impairment and these seven different areas that's what we're funding right so that's the complement to that amyloid so when I said uh tomorrow's answers today that's what we're talking about and I can sure every person sitting here those of you that have funded us the last five years have brought us to this moment those of you that are funding us now it's those non-amyloid trials so that okay we'll put you on the combination avoid and inflammation we'll put you on the camel the the amyloid and the combination of some vascular issues that whole field exists because of Howard and the addf and you thank you they'll be here for some more questions one-on-one so thank you

Channel: Alzheimer's Drug Discovery Foundation

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Id: jtAWyq0TMbw

Length: 80min 51sec (4851 seconds)

Published: Wed Jan 25 2023