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National Institutes of Health
National Institute on Aging
Alzheimer’s Disease Research Summit 2012: Path to Treatment and Prevention
May 14–15, 2012
Natcher Auditorium, NIH Campus, Bethesda, Maryland
Neil Buckholtz, Ph.D. (Chief of the Dementias of Aging Branch of the Neuroscience and Neuropsychology of Aging Program at the National Institute on Aging at NIH):
If you could please be seated. It is my pleasure this morning to introduce the director of the NIH, Dr. Francis Collins.
Francis Collins, MD. Ph.D. (Director, National Institutes of Health):
Good morning to all of you.I am delighted thattoday has come, and I know many peoplehave worked very hard to makethis summit possible. You andI have high expectations for this kind of scientificdiscussion and opportunities for debate about the trajectory for researchon Alzheimer’s disease, a disorderthat we all agree deserves our intense attention overthe next day and a half as we seekto identify, in this remarkablemoment, how to make the mostof the research advancesthat seem now to be possible to try to do somethingaboutthis really seriouscircumstance now with morethan 5 millionpeople affected with Alzheimer’s disease, and with the cost of caring for them approaching $200 billion a year. The trajectory that one sees if nothing happens, given theaging of the population,could become an even greater disaster for individuals, families, caregivers, andour whole nation. So, the importance of the problem can hardly be overstated.And yet, there is among all of us, I think, a sense of optimismthat we havescientific opportunities emergingnow which perhaps we might not haveimagined could come along so quickly,and now give us a realsense of progress in this area andan opportunity to accelerate that.
I do think there area number ofscientific developments in the lasttwomonths that are deserving of attentionfor a moment here, and I’m sure they willbe highlighted in the course of the next day and ahalf. For me, as the director of theNIH, one of the remarkable experiencesis to beable to survey allthat is happening in biomedicalresearch on any given Monday orTuesday and see what new developments have suddenly emerged. I have to saythat forAlzheimer’s disease, it has beena remarkable ride over just thelast few months. That builds uponmany efforts that many of you havebeen carrying outover many years.
I don’t meant to imply this bursts out of nowhere, because there has beena lot of workto get us to this point, including enormousamounts of effort that involved buildingof teams, publicand private partnerships, and many other components to get us where weare. I can single out, for instance,some of the things that wehave learned about the effect ofAlzheimer’s on the brain basedon imaging capabilities that haveallowed us to see these advances earlierthan we probably dreamed possible.
Certainly thepublic-private partnership, theADNI Alzheimer’s Disease Neuroimaging Initiative, a very important partnership with industry, has been a critical part of getting us to that point. And I think it is pointed to bypeople outside of this field andacross many different fields asa great exampleof how industry and academia andNIH can work together toadvance the field, making data broadly accessiblethat otherwise would nothave been within reach. These advances inimaginghave led to the ability between NIA andthe Alzheimer’s Association to revisediagnostic guidelines for the firsttime in 27 years. This is areally valuable step forward.
In another area – genetics – the ability, by utilizingnew maps of human variation,to scan the entire genome and look for additionalrisk factors for Alzheimer’sdisease going beyond the well-established ApoE4effect has led us to atleast four additionalrisk factor genes, with othersunderscrutiny. This progress is pointing us topathwaysinvolving inflammation and lipidmetabolism, which I might not necessarilyhave known about were it not forthe lens thatthe genome-wide association studies have now providedin giving us new clues in termsofpathogenesis and ultimately meansof prevention and treatment.
I thinkour basic understanding of how Alzheimer’saffects thebrain has certainly made severaladvances in just the last few months.Certainly, this recent realizationthat the TAU proteinis in factspreading fromneuron to neuron, as opposed tobeing produced entirelyin an endogenous, cell-specific way, is a revelation that most peoplewere not expecting in terms of understandingthe pathogenesis, and gives a window into how to stop that spread. Neurons arenot just committing suicide.They’re also committing homicideon their neighbors, and if we can figure out how to stop that atatime where TAU ispassing from one cell to the next, that would be a remarkable, exciting newdirection to go.
Along with that is our ability to use this newtechnology of inducedpluripotent stem cells to derive cells fromindividualswho have Alzheimer’s disease of the dominantlyinherited form, the sporadic form,or normal controls, and showing,as was recently done, that there are differences between those cells if they’re differentiated in the cortical neurons that provide asignature that may give us cluesto pathogenesis andmay also provide an opportunityfor direct screening of drug compoundsthat couldbe seen if they have benefit againstthat cellular phenotype.
That againis not something a few years ago we could haveimagined possible, and now here it is with all the potentialthat carries for follow-ups.
In terms of translationalresearch, what we’ve learnedabout the basic science of Alzheimer’sand moving forward toward therapeuticsorpreventive strategies: Since 2006, NIH has funded close to 60Alzheimer’sdisease translational research projects that supportearly drug discovery andpreclinical drug development. With the establishment of the newNational Center forAdvancing Translational Sciences(NCATS), there is another partneron the scene here that may be able to assistin dealing with someof the bottlenecks that otherwisehave vexed the process of developingtherapeutics for lots of diseases,including this one. One thing that NCATS wasable to achieve 10 days ago wasan agreement among three pharmaceuticalcompanies—Pfizer, Lily, and Astra Zeneca—to open their freezers and make compounds availablefor new applications thathave already been in human subjectsas part of clinical trials, butturned out notto be effective for the diseasethey were being tested against.That list of compounds will beavailable in June andinvestigators can then make applicationif they have a new idea about howto use those compounds fora different disease.
Arrangementscan then be made with standard templatesabout how to set that research programup, and NIH, in theform of NCATS, is setting aside $20 million nextyear to supportthose repurposing efforts, including a bitof preclinical study. But onecan go almost immediately to a Phase II trial, because these are compounds known in humans with a lot of informationabout their pharmacokinetics.
So thatis a potential shortcut in theefforts to develop new therapeutics that’s worth paying attentionto, and we’re expecting other companiesto join thiseffort as well. Having seen thatlist, I can tell you that many ofthesecompounds do cross the blood-brain barrier, andtherefore may be of interest topeople in this audience.
If youthink it seems unlikely that that kind of drug repositioning would be beneficialfor diseases like Alzheimer’s, whichhas been challenging to attack,then I would point you to that recent,remarkable paper in Science.Work on the mouse model ofAlzheimer’s disease showedthat a drug developed, actuallynot for a brain disease, but for T-celllymphoma, the drug called [bactherapine], when given to the mouse model, iscapable of reducingthe amount of amyloid in the brain by about50 percent injust 72 hours, which isa truly remarkable result, and also showed improvement in mouse performanceas a consequence. Whether that mousemodel is a favorably well-designedone for human disease is somethingI’m sure that will be discussedand probably argued a bitin the course of thismeeting, but you can’t look at theresult without feeling energized aboutwhat it might say. It also tellsus something about howAPOE plays a role inthe disease, because after knowingabout the genetic risk from the ApoE4 allele,we’ve been arguing about exactlyhow that plays a role in disease. This particular study shed new light on that.
In terms of clinical trials—which is where I think ultimatelywe hope to see this field go—with compoundsthat show clear evidence ofactivity in cell models or animalmodels—we want to try to speed the processof getting those into clinical trialsandto do so in a way that has the maximum likelihood ofyielding meaningful results. This certainlymeans that weare going to need to focus carefullyon which kinds of patient populationsare most likely to give us the informationwe need. And probably, individuals with faradvanced disease are going to be verychallenging, and we may need to thinkmuch harder about how to design trialsthat are basicallyenrolling individuals very earlyin the course, perhaps even beforemuch in the way of symptomshas appeared. People have argued, for instance, that if you were testing patients to see what was beneficial for cardiovascular disease, you would not test with far-advanced congestive heart failurebecause it would be unlikely tosee much benefit. Likewise withAlzheimer’s, we need to figureout where is the best window ofopportunity for testing therapiesthat will be talked about.
Therecent pilotstudy—one we’re excited about but needs to be expanded—using a nasal spray form of insulin, which showed adelay in memory loss and preservingcognition, is one example of a newidea thatclearly deserves additional work.For obvious reasons, given thepublic health urgency and the scientificopportunity,with much leadership from RichardHodes, the remarkablydedicated leader of the NationalInstitute onAging, and others, NIH has steppedup ina fairly unprecedented way to make Alzheimer’sdisease a very high priorityfor our research agenda.
We did announce that this currentfiscalyear will include theidentification of an additional $15million for Alzheimer’s disease researchthat otherwise would not have beenpart of the usual scheme of things.Because this is not a time for theusual scheme of things. In the President’sbudget, as you heard announceda couple of months ago, there is anadditional proposal of $80 millionin FY 13 to be utilized to accelerateAlzheimer’s disease research. Tomorrow at 10:30a.m., my boss, Secretary Kathleen Sebelius, will be here becauseshe wanted to cometo this meeting to talk about theAlzheimer’s research plan and specificallyto say something about how we’regoing to utilize those $50 millionof extra research support in thecurrent fiscalyear. So I won’t steal her thunderby telling you exactly whatthose proposals for grant funding are going to be, but they are now where they can be stated publicly by her tomorrow.So come for that. I suspect you probably will.
Again, I am delightedto be here. I want tothank Richard and the others who have workedso hard on this. I want to thankthe advocates for Alzheimer’s diseasewho have tirelessly put forwardthe case of why this is a time wherewe asa nation need to take vigorous actionto address this problem. I wanttothank the scientists who have madethis possible by your work overthe course of many years to getus to the point where I think wecan collectively see a real inflectionpoint, having arrived where we might be able to accelerate progress ina way that offers real hopeto those who are affected. I mostlywant to thank thosewho are advocatesthemselves and also caregivers, for your dedication to this topicand to your families, and for the hope you’veplaced in this meeting and otherslike it to try to find answers.It is toyou that we dedicate our effortstoday and tomorrow and going forward.Thank youverymuch.
Richard J. Hodes, M.D. (Director, National Institute on Aging at NIH):
I would like to addmy own thanks to all of youfor your participation in this momentousmeeting. The factthat we have oversubscribed the registrationin this, our largest venue at NIH,is a tribute tothe depth and breadth of commitmentto the importance of this program. And I’m happy to say we have webcasting that will allow us to transmit the proceedings even further, and that weare joined by themedia, who willalso helpedto propagate this.
Therepresentation of the meeting hereis reflective of the broad constituenciesthat understand that Alzheimer’sresearch aimed attreatment and prevention is an internationalgroup that includes academics, industry, and private-sectoradvocates, and perhaps most of allthose who share a commitment tofamily and loved ones who are affectedor may someday be affected bythis devastating disease. There hasbeen a lot of work done in the backgroundbefore this meeting thatI want to acknowledge as well. All ofthe sessionchairs and the speakers and thediscussants have had multiple pre-meetingsto stage the frameworkfor the conversation we’re having. That conversation willoccur here, and I also want to note, as you see in the agenda, that a substantial time is permittedineach sessionfor participation by the audience, input that is extremely important.
NeilBuckholtz, who I will thank andintroduce in a moment,will probably be the strongarm who will be responsible formaking sure that we discipline the inputso as many people as possible havea chance to have thatinput. In addition to the workof the meetingparticipants, other background hasincluded the collaboration of theAlzheimer’s Associationand the National Institute onAging on generating an ontologythat is a formulation ofthe terminology for the first time that will allowall who support and monitor agingresearch to understandthe breadth of that research incategories that are meaningful andwith that information tomaximize the interaction and efficiencyand minimize the number of gapsor unnecessary duplications thatoccur. I’m happy to announcethat last year this disease researchinventory was posted, and you can finditon the NIA.NIH.GOV website. Overthenext months, it will be transmittedinto a database that will be all the moreefficient.
Rightnow it includes all the research from NIH, other Federal agencies, and the Alzheimer’s Association. It will grow to become an international resource. The meeting we arehere for today, as Francis noted,is an important part in the missionthat was laid out in the NationalAlzheimer’s Project Act,which will commission the releasetomorrow ofthe first National Alzheimer’s Plan.
It is most critical that the plan be implementedwith the best judgment and scienceas determined by experts. So we’re enormously pleased to be ableto have the advantage of the intellect, the experience, and the perspectivesof all ofyou here participating in this meeting to allowthis to serve as,in the very most effective way,what we are all committedto next: theimplementation, with all due haste and efficiencyin our translation, of the mostbasic of research into the interventionsthat are the goal for all of us.Iwill now take a delight in thankinga number of people who have beenmost critical inthe background of this meeting.Many of you have heard from Tamara Jones, who has worked tirelesslywith you, as wellas the Department, and those involved in sponsorship, as has beennoted,NeilBuckholtz has been a greatleader, not just information of thissummit, but in fact in Alzheimer’s researchacross the nation over thesepast years.
So my next great pleasure isto introduce NeilBuckholtz, who will tell you how the meeting will proceed. Welcome,and I look forward to sharing withyou the excitement over the next twodays.
Neil Buckholtz:
Thank you, Richard. There are a numberof people who have worked very hardto make this meeting areality. I would like to give specialrecognition and thanks for theirtireless effortsto my colleagues, Suzana Petanceska,Bruce Elliot, and Tamara Jones at the NationalInstitute on Aging. And Erika Tarver, Andrea Pritchett, and JoshWalker at the Foundation for NIH.
I have a number of housekeepingand procedural announcements tomake. First of all, the restroomsareat either side—very critical aspects—outside the auditorium.Secondly, please keep your badges forDay Two. As you may have noticed from theagenda, we havenot put any specific breaks inbecause there was really no efficient wayto get more than 600 people in andout of the auditorium ina reasonable time. So please feel freeto take a break whenever you needto. There will be light refreshmentsoutsidethe auditorium in the morningand afternoon starting at 9:00 a.m.These products have been provided throughprivate donations to the Foundationfor NIH. No
Federal fundshave been used for the food. At theregistration table, there are boxlunchesavailablefor purchase.They will be available at tablesoutside the auditorium to pick upatthe lunch break. However it’s importantto note that there is no food ordrink allowedin the Natcher auditorium.
To each of thesessions, the chair will introducethe topic in a 5-minutetime period, then the chair willintroduce each of the speakers forhis or her15-minute talk. Speakers will thengo back down totheir seats. After the talks, there’llbe a number of formal discussantswho will have5 minutesto address a specific aspect related to the topic of thesession. If the discussion is not doneby his or her 5 minutes, the Summit slide willcome on, indicating we need to goon to the next person. Iwill ask the formal discussants to comeonto the stage all at onceafter the last speaker ofthe session. And then after the discussantsare finished, I would ask the speakersto come up to the table throughthe open partof the discussion.
We have provided, as Richard indicated,an open discussion period aftereach of the sessions. Butbecause of the large number of peopleattending the Summit, we have a 2-minutelimit for questions or commentsfromthe audience. This will be enforcedbythe session chairs. There are simplytoo many people present forlengthy comments. For those of youin the balcony, you can come downto the auditorium if you wouldlike to make a comment orask a question.