Roundtable Discussion with Alzheimer's Fast Track 2019 Co-Chairs

Co-chairs of the Alzheimer's Fast Track program discuss big challenges that need to be tackled worldwide: Remaining steadfastly committed to funding Alzheimer's disease and related dementias research; Supporting innovative, early-career investigators; Encouraging researchers from under-represented groups who are disproportionately affected by Alzheimer’s to lead independent research labs; and the future of clinical trials, treatments and finding a cure.


Transcript:

Diane Bovenkamp, PhD: My name is Diane Bovenkamp, I'm the Vice President of Scientific Affairs with BrightFocus Foundation, and I'm here with the co-chairs of the BrightFocus Alzheimer's Fast Track to discuss some very important topics for Alzheimer's disease and related dementia today. So, Harry, can you introduce yourself?

Harry Steinbusch, PhD: My name is—yes of course—my name is Professor Harry Steinbusch, I'm from Maastricht University in the Netherlands in Europe, and I'm involved here to really, to really study the different aspects of Alzheimer's research in relation to co-morbidities, and I'll explain that later in more detail.

Frank LaFerla, PhD: I'm Frank LaFerla, I'm the Dean of the School of Biological Sciences at the University of California, Irvine.

Cynthia Lemere, PhD: I'm Cindy Lemere, I work at Brigham and Women's Hospital in the Ann Romney Center for Neurologic Diseases and hold a position on the faculty at Harvard Medical School in Boston.

Diane Bovenkamp, PhD: All right, so I'll just get right into it, the first question I have here is, is there a role for non-profits and institutions to support early career researchers?

Frank LaFerla, PhD: Absolutely. We need that, we need the non-profits to help cultivate and raise the next generation of researchers.

Cynthia Lemere, PhD: And I also think that at this time, there is tremendous opportunity through institutions but especially through foundations, many foundations, because of this increase in funding to NIH for Alzheimer's disease, many foundations and associations are now funding young investigators. So at this point I think it's really cool that many foundations and associations are really putting their efforts into helping young investigators transition in their careers, how to start their own labs and really move along that career path.

Diane Bovenkamp, PhD: Yeah, because I know especially what we're doing here today, I mean, the four of us and the three of you in particular have been involved for like a decade and more and doing the BrightFocus Alzheimer's Fast Track, which is essentially a master class for not only understanding what are all the relevant topics in Alzheimer's, but to help train them with how to write a grant and how to network. And yeah, at BrightFocus we have postdoctoral fellowships, but yeah, we like to have the Fast Track to try and help them.

Frank LaFerla, PhD: I mean I guess the bottom line, the bottom line for me is we need more scientifically trained people in the world, not less right? Carl Sagan has this great quote that says that we live in a society exquisitely dependent on science and technology, which hardly anyone knows anything about science and technology. And so, for these you know major scourges and challenges they're only going to be solved by the next generation of scientists.

Harry Steinbusch, PhD: Yeah so, I would like to answer that it's basically not a necessity. It's essential that we have funding available from non-profits and why. We see we still haven't yet, at least I think, not a real cure for Alzheimer's disease. In addition, we see a sharp increase coming up of people who are suffering from Alzheimer's disease so we need much more funding in the future from organizations like non-profit organizations who have funding for young researchers to enter the field, to also pursue a scientific career in this disease.

Frank LaFerla, PhD: And I could add one more point, I guess, and it's that we're in a war, right? And we need everyone to participate to help us win this war. The government has a role to play but private individuals do as well, in helping to donate and fund research so we can move the field forward.

Diane Bovenkamp, PhD: Yeah, and disease has no borders. People from all countries all over the world have Alzheimer's disease and related dementia and so, you know, our organization has made a choice that there is no, we funded in 24 countries, so there's no citizenship requirement so, we go anywhere where we can find the next best idea for a cure.

Frank LaFerla, PhD: And that's one of the great things about the Fast Track, right, is that it brings together people from all over the global community.

Diane Bovenkamp, PhD: Absolutely.

Frank LaFerla, PhD: Harry’s from the Netherlands.

Harry Steinbusch, PhD: And we had more people from Europe here, we had people here from Korea who also like to participate, so it's a global effort and my focus is to really challenge a global effort in pursuing new scientists entering the field of Alzheimer's.

Frank LaFerla, PhD: That's a good point here.

Diane Bovenkamp, PhD: And researchers as well as clinician researchers, because there's a need for people to be, for clinicians and clinician scientists, to be leading all of the clinical trials, you know, taking care of patients. So, another question here is, are there ideas that could be pursued to encourage minorities and women who are, and underrepresented groups, who are disproportionately impacted by Alzheimer's, to help them lead independent research labs?

Frank LaFerla, PhD: Absolutely I mean we know that diverse people create diverse ideas, and we know that for complex you know problems like Alzheimer's it's only going to be solved through diverse approaches, and one of the things that's needed, are role models, and it's pretty clear just like women needed women role models to encourage them to go into science, I think the same thing is true for other minorities. They need to have role models. So, we and our institutions need to collectively do a much better job encouraging them to go and consider a scientific career. As a matter of fact, I think one of the things you're going to see, a big sea change, is in terms of college rankings. They're going to, now for the first time, really consider the impact on social mobility; how good are universities of giving opportunities from people from underprivileged classes the opportunity to get an education.

Diane Bovenkamp, PhD: So, what we're seeing right now is almost a reflection of the access to education 10 years ago. Yeah, and so if we can make a change now.

Cynthia Lemere, PhD: I also think that one way to do this is to help encourage the scientists, but also to have those scientists then go out and engage with the community and really bring education and bring awareness of Alzheimer's disease out to the community, and in a more global effort. It's a global problem so we need global effort.

Harry Steinbusch, PhD: Well, we see similar and even, even more challenging changes in Europe. In three countries, which is Sweden, the Netherlands, but also in Norway, to increase the proportion of women in science. Both the Netherlands and in Sweden, they took a drastic step, maybe you'd like it a lot, on Dutch university in Swedish universities for one year. No men are attracted anymore. So all positions are filled with only women. There was a lot of protest by Dutch men, but the government said we tried it for years, it doesn't work. Now we do it drastically, January 1st next year till January 1st 2021, there are no positions open for men.

Diane Bovenkamp, PhD: Those are in those three countries?

Harry Steinbusch, PhD: Yes, and this is a lot of discussion but they said we really would like to come to this increase. Still in those two countries, the percentage between women and men in science it's about 22% for women and 78% for men, and the government wants to bring it to 40:60.

Diane Bovenkamp, PhD: So, you're mentioning, I mean it's the funding agencies and the institutions and the scientists, but you also need the government involvement and-

Harry Steinbusch, PhD: Absolutely.

Diane Bovenkamp, PhD: The government is voted in by the people and so yeah, so everybody needs to move forward.

Harry Steinbusch, PhD: So, we really can see that as a transition, the transition is already clear if you look to our first and second year university students the majority are women. It’s 70%, 72%. So basically in the long run there will be more movement, but it takes too long and the government has decided you know they would like to push it quickly now.

Frank LaFerla, PhD: I think the same thing is true in the United States where at the lower levels you see many more women—on the higher percentage of women than men but then as you go up the ranks then the numbers reverse.

Diane Bovenkamp, PhD: Yeah and I think that there are some programs that have, that are being developed and may be available now and more in the future for increasing awareness, helping with the training and retention of, and a lot of that too also has to do with supporting not just women, but men and women you know, in you know, if family is an issue that might make people self-select, drop out, then we need to create some kind of support network that, you know, that people will feel like they can still pursue.

Cynthia Lemere, PhD: So, it is, I think the big thing now, is that increasingly there are more and more females represented in faculty at least in the U.S. I would say that's pretty true. But you're right, as you go to the higher levels there are fewer and fewer women, the percent's really drop. But part of that is because it takes a while to get there so you look back 30 years and the number of females that were actually trying to go in that track, you may have started out high but really dropped. And in my own career I've seen women go through, you know trying to make it, and making decisions to do something else or, and it doesn't necessarily mean dropping out of the workforce or dropping out of a career in academic medicine. I've had people train in my lab that went on to do other things, like become scientific writers, which has a lot more flexibility. So, it's not necessarily true that everyone's dropping out, that you know, they're not pursuing a career anymore, but they may find different careers.

Frank LaFerla, PhD: Or in academia.

Cynthia Lemere, PhD: Yeah.

Frank LaFerla, PhD: I mean it could be implicit bias, right? How women are traditionally not good at selling themselves the way men are. I mean I know my daughter went, you know, applied to medical school and it was just so interesting to see the way she filled out the application and responded to questions the way I would have done it, even though she was incredibly talented, and you know they say that you know men, if they have you know six out of ten you know quality, you know attributes, where the qualifications for a job apply, women don't apply unless they have like 9.8, right.

Diane Bovenkamp, PhD: Yeah

Frank LaFerla, PhD: And so, and I said with that, with my own daughter it's very interesting.

Diane Bovenkamp, PhD: Yeah, and I mean like BrightFocus is, you know, and many other funders, have been you know, we know there is research out there that you know, we try and make sure that we don't have you know, that we comb through our, the wording of our RFPs, and we make sure that we don't put in wording that can make someone self-select and not apply. We also try and just always have reminders of, you know, our review committees to just be self-aware of implicit bias, and so it's also like vigilance, you know, to try. Yeah, all right, so the next question I guess I'll put out there for a discussion is, what is the biggest scientific question in Alzheimer's that scientists, clinicians, well researchers will have to tackle in their careers?

Harry Steinbusch, PhD: In their careers?

Diane Bovenkamp, PhD: Yeah, in our lifetime I guess.

Frank LaFerla, PhD: The biggest of them all is, you know, what's it going to take to get a cure for Alzheimer's disease and eliminate this as a scourge for mankind, right? That's probably the biggest, you know. Then of course everyone's taken their own approaches to trying to contribute towards that ultimate goal. I mean that would be my response.

Cynthia Lemere, PhD: I would say I agree with that, but I also think really, clearly understanding what causes the disease and finding approaches that might prevent it at the beginning, but also ways to slow the progression or ultimately reverse the disease.

Harry Steinbusch, PhD: So, we'd like to, the Netherlands at least, we have some discussion about this question and we would like to bring it down to smaller questions. So, if you say what we have to find a pill for Alzheimer’s, that question is too big. If we say we have to, we have to find preventive mechanisms, even that equation is too big. So, we like to focus a lot about what's, what has been, how has the research developed in another field like cancer research and how do they find treatments in cancer research and what can be learned from that approach. Now we took that question and went back to Alzheimer’s, and first we started to diverse the field of Alzheimer’s in about 47, 46 different subunits, and then we investigated quite a lot at the moment: can we find repurposing drugs? As a different word for you, between purpose and works means that we use drugs which are already recognized by the NDA. For other purposes in cancer research, they have been tested for toxic effects, and we're going to use some of these drugs in these 46 different sub categories, and we defined, do they have any effects? That's one thing. Secondly and the most important thing, and now I speak for Europe because we have some discussion about that too is, and that's my topic of course, it's core mobility. If we don't have a drug for Alzheimer’s, what can we do elsewhere to guarantee and to increase the quality of life of people who are suffering with Alzheimer's disease? So, we like to do a lot of these side studies and to see, can we increase the quality of life of patients? That's basically it. And on the parallel, we have of course the big question. So, the big question is, can we find a treatment for Alzheimer's disease? So, all these questions are important to us.

Diane Bovenkamp, PhD: And the other area that really needs to be addressed and it's come to like a critical head with a number of clinical trials just not meeting primary endpoints is, you know, are currently are the guidelines, are we recruiting the right people into clinical trials? And so, I think that the answer is no. They're finding that, you know, it's all mixed ideology. So, there's a, current standard for biomarkers or differential diagnosis, we might be recruiting the wrong people into clinical trials, and so there needs to be further studies on that, so that then if we actually do find the right drug, we're just, it's not so that it can actually make it to the market and it's not just getting shut down because it missed a primary endpoint.

Frank LaFerla, PhD: I guess it's remarkable how much more work we still have ahead of us.

Diane Bovenkamp, PhD: Yeah.

Frank LaFerla, PhD: To understand this disease, right.

Diane Bovenkamp, PhD: Yeah.

Harry Steinbusch, PhD: And that's why we need funding from the nonprofit organizations, to have, to attract people who join the field. It's essential.

Frank LaFerla, PhD: Yeah.

Cynthia Lemere, PhD: And especially for new and bold ideas, I think there's a really special role for foundations to allow the, what's the word -

Frank LaFerla, PhD: Non-incremental science, these really bold, real high-risk projects.

Cynthia Lemere, PhD: But to really take a chance and really try to look at something in a completely new light, bring in new investigators from other fields, and really you know do these pilot projects that might otherwise not be funded by the larger institutions like NIH, because they're too risky.

Diane Bovenkamp, PhD: It only takes one idea to get, to get forward for effective treatment.

Frank LaFerla, PhD: You know I think one of the things you know if I look back in hindsight at the whole field, we've taken this incredibly reductionistic approach to a complex disorder like Alzheimer's, and I think as neurobiologists, we think of the brain that's so special that we forget that it's connected to the rest of the body and that's what Harry's been saying: that these comorbidities matter. So, and in part it was led by the revolution in molecular biology right? We thought that we were going to understand how the body works and how disease happens just by knowing the DNA sequence of genes involved in all of these disorders, and you know it wasn't enough even in Alzheimer's to, you know, not only do we only look focused on the brain, but within the brain, we only focus on the hippocampus, you know if you look at some other region, God forbid, it was like why are you looking at anything other than the hippocampus? And now I think we're seeing that the field is reacting to that and taking a much more holistic integrative approach, because everything is interconnected right? We know that even the microbiome seems to have backfired.

Harry Steinbusch, PhD: Yes.

Cynthia Lemere, PhD: And then ultimately there are sex differences as well, and that a treatment may be one thing for a female and a different thing for a male. So, I think that this whole idea of personalized medicine or precision medicine, is really, really -

Diane Bovenkamp, PhD: In different populations, yeah, right.

Cynthia Lemere, PhD: - gaining speed now in different populations. Yeah, it really is very, very important to keep in mind, and that's going to be a further complication I think for clinical trials but ultimately, it'll probably get us to where we need to be to find effective treatments.

Diane Bovenkamp, PhD: I have a lot of hope.

Frank LaFerla, PhD: Yeah, I do too.

Diane Bovenkamp, PhD: Yeah, yeah.

Frank LaFerla, PhD: And research equals hope, there's no doubt about it.

Diane Bovenkamp, PhD: So, I guess this is our last question here. After decades of effort without a commercially available disease modifying treatment for Alzheimer's disease or related dementias, help us explain why we need our donors to remain committed to supporting Alzheimer's disease?

Frank LaFerla, PhD: Well, we still have people that are impacted by Alzheimer's disease, and we probably will for the foreseeable future, and so until that, you know, changes we're going to constantly need to be researching and developing new diagnostic methods, new research into potential therapies, better understanding of the mechanism of action, and that's going to require funding to support research and new investigators. Yeah, it's going to have to continue until this disease is itself a memory.

Cynthia Lemere, PhD: And I would say just to add to that Alzheimer's is not going away, and if anything, it's affecting more and more people. At this point now they're in the U.S. alone, they're about 5.6 million people with Alzheimer's. That number is expected to grow to 14 million by 2050. The cost to the population in the government is extremely high. The health care system is not ready to handle that type of health load, I would say. So, this is, if anything, we need more researchers, we need to train more young people, get them involved, get them motivated to try to tackle this problem. This is a growing problem, it's not going to go away.

Frank LaFerla, PhD: We need more, not less right.

Cynthia Lemere, PhD: Yeah.

Frank LaFerla, PhD: I mean in the United States right now, it's one out of every five Medicare dollars goes to care and treat Alzheimer's patients and by the middle of the century, it's going to be one out of every three Medicare dollars.

Diane Bovenkamp, PhD: Yeah, I think people have been saying it could bankrupt the entire health care system.

Frank LaFerla, PhD: Absolutely. Talking about trillions of dollars on a national level and when you, I mean you're on the board, what's the statistic right now? It's like one person develops Alzheimer's every 65 seconds or so in the United States.

Diane Bovenkamp, PhD: Yeah.

Frank LaFerla, PhD: It's crazy.

Diane Bovenkamp, PhD: Yeah.

Frank LaFerla, PhD: And by mid-century it's supposed to be one out of every 33 seconds or so.

Harry Steinbusch, PhD: I don't believe we will have one pill for Alzheimer's. We will have a combi therapy like we see also with HIV, so we have a therapy which we use which we're going to treat different, different parts of Alzheimer's and different forms, and that needs further research. We need, we will see already in I think also here in the U.S., the increase in Alzheimer's is less sharp as we had expected. It's a little bit, it's not going downwards, but it's simply not as sharp as we thought because of the changes in the lifestyle of the people. People are changing, diets are changing. I'm not sure in the U.S. because I must confess, I can see a lot of people here with obesity and we're also going to look, what role of obesity does in AD, That's another project which will be, what is the role of the environment on AD? What is the role of stress-related events? What people have in our society at the moment? So, we do have a lot of challenges in which we need funding for to pursue.

Diane Bovenkamp, PhD: And we can't just give up, I mean, we have to almost double down, and like what you said, research equals hope and we need we need more funds to help, you know, encourage these innovative ideas, attract young investigators, and retain them in the field, and so that we can serve, you know, the families affected by this devastating disease.

Frank LaFerla, PhD: I mean treatment or cure is only going to come through research. Wishing and hoping is not going to get us there.

Harry Steinbusch, PhD: It's not a choice between treatment and cure. It's treatment and cure. Treatment, cure, and care. You all need them. So basically, for me, the most important part is that we have to bring it more to a personalized level. We have in Europe, the big discussion about immigration. We got a big administration from the Mediterranean. and from Africa, of course. Questions which are coming there is, do we have to treat also people with a genetic differ—with a different genetic background in a different way, related to Alzheimer's. That's do we have different care houses for different populations. All these questions are there, important.

Diane Bovenkamp, PhD: Yeah, and disease has no borders. It's a global, global situation.

This content was first posted on: November 10, 2020
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