Bart de Strooper, of Katholieke Universiteit Leuven, has been named to direct the United Kingdom’s £250 million Dementia Research Institute (DRI), to be based at University College London. De Strooper, who currently co-directs the Flanders Institute of Biotechnology’s Center for the Biology of Disease in Leuven, will assume his new role in January 2017.

Bart De Strooper

Plans for the DRI grew out of Prime Minister David Cameron’s challenge on dementia 2020, and the U.K. MRC subsequently partnered with the charities Alzheimer’s Research U.K. and Alzheimer’s Society to pledge a quarter-billion pounds toward it (see May 2016 news). Alzforum readers have gotten to know De Strooper’s research and penchant for challenging hypotheses in the field. What is his vision for a new 400-person institute? Find out in this Q&A, and nab a little contemporary perspective on solanezumab along the way. Questions by Gabrielle Strobel.

Q: Congrats. Was this an easy decision?

A: I was hesitating. We have a fantastic institute with young researchers here in Leuven, and I also really enjoyed combining scientific and organizational work while directing our department for the past 10 years. And there’s Brexit. But the DRI is another dimension, and comes with the ability to tap into the U.K.’s world-class dementia research. In the end, it was my wife who said, “This the job for you.”

Q: And you listened to her.

A: I listen a lot to my wife! She is a wise woman.

Q: What about your positions at KUL and VIB? Will you move to London full time?

A: Almost. I resigned my director and chairman positions and most other professional engagements. With UCL’s agreement, I will, however, continue supervising people in my research group here in Leuven and help advance dementia research in Leuven. I will keep the lab complete for at least the next two years and then we will see what parts are transferring to London and what parts stay in Leuven.

Q: How will that work?

A: I will spend four days a week in London and three days a week in Leuven. The first year my focus will be to start the DRI. We will recruit at least 25 independent group leaders through an international call. For my own research, I will build a second lab in London. That’s all feasible because the train from London to Leuven takes only 2½ hours. And it could be good for dementia research to create links between London and Leuven.

Q: Is the £250 million pounds a startup package?

A: It is the budget for the next seven years. DRI will spend about £32 million per year, plus there will be funding to build an iconic building for dementia research in London. I hope many other charities will join the MRC, ARUK, and Alzheimer’s Society, particularly for Parkinson’s and frontotemporal dementias, amyotrophic lateral sclerosis, Huntington’s, and maybe other triplet-repeat diseases. It makes sense to tackle all this in one institute because of the mechanistic overlap across these diseases. On the shared proteopathic aspects, and the shared problem of translating genetics to mechanism with good animal models, we can learn from each other and save time by not repeating mistakes.

Q: Is the DRI the only institute dedicated to dementia research? And will it reorganize or add to existing dementia research?

A: It will be unique, a national institute. There already is a lot of dementia research in the U.K., which I expect will continue because the promise to me was that the £250 million is new money. That has been made very clear. I will have to watch for that. These funds over seven years only begin to close the gap to cancer and AIDS funding. It would be a mistake for the government and other funders to think they have done their job.

Q: How will the DRI fit in with other dementia research initiatives in the U.K.?

A: I see it as a piece in a larger jigsaw puzzle. For example, the U.K. has the Dementias Platform U.K., and big ongoing clinical studies. It also has natural history cohorts and a lot of human genetics studies. ARUK has invested in an alliance of three drug discovery institutes (see Feb 2015 news). I hope all this will continue. My priority will be mechanism-oriented research, where we try to understand what goes wrong in the brain and find new drug targets. The U.K. is ready to test drugs in patients; we need a greater variety of drugs ready for testing.

Q: How about the Dementia Discovery Fund?

A: DRI is independent of this investment fund. We will want to partner with them once we have things that come close to practical application.

Q: What is the DRI’s relationship to University College London?

A: UCL hosts DRI’s hub, but the DRI is broader. We will do a call for up to six other centers for dementia research; all those together will form the DRI.

Q: So organizationally, the DRI resembles Germany’s DZNE, with its hub in Bonn and multiple centers in cities across the country?

A: Yes, or like Belgium’s VIB, where Ghent anchors a handful of strong centers elsewhere. The VIB is all biotech, and DRI focuses on dementia, so the scale of the dementia research effort in the U.K. is larger. We hope to mobilize existing dementia research at universities across the U.K. and to motivate others to interact and collaborate with us. The DRI will not have a monopoly on U.K. dementia research.

Q: Where are the other centers?

A: That is still a secret. Eight universities have already undergone considerable scrutiny competing to be the hub. They now have the chance to become a center. It’s a long process. We first pay a founding grant. With it, a candidate center identifies a director who wants to take a leadership role beyond their own research, and adds up to four professors at that university to form a founding group. One year later, the group gets additional money to attract new people to the center. So the application has to articulate a growth vision, and in the next two to three years there will be plenty of group leader positions in the U.K.

Q: So the centers are in this process now. What is your role in the choice?

A: I wrote a vision about the DRI and will look for applications that reflect this vision, but the final decision belongs to our international panel of peers.

Q: Why did UCL win the bid for hub?

A: They are the largest in the U.K. in both neuroscience and dementia science. Strong competing bids from Oxford, Cambridge, King’s College, and Edinburgh made it a difficult decision. Currently eight centers are competing for four to six spots.

Q: Was the cellular phase of AD on your mind when you framed your vision for the DRI (see Mar 2016 webinar)? 

A: Yes, I want to do mechanistic work around the ideas of the cellular phase of AD—and expand it to other dementias. Last week I got all these media questions about the amyloid hypothesis after the solanezumab Expedition 3 failure, and I think we urgently need to go beyond the amyloid hypothesis.

Q: Explain.

A: It is 25 years old. It was then a good summary of what was known at the time. Now we know things are much more complicated. Even just within Aβ, there are many more species than Aβ42, plus the linear relationship between Aβ and tau is unclear. I think we are evolving to the understanding that it takes multiple hits before the brain—this plastic, resilient, wonderful organ—breaks down. We know that is true in cancer.

Q: A multiple-hit hypotheses has been articulated in AD.

A: We should be much more open to it. In my view, there are several pathways and we need better statistics about how many are needed in AD. We could take cues from a paper in ALS that claims you need at least five independent hits before someone gets ALS (Al-Chalabi et al, 2014). I think it is the same with AD and PD. If you think that way, then the solanezumab Expedition data makes more sense. If you remove one hit, i.e. amyloid, and it’s early on and no other hits are operative, then you can perhaps avoid Alzheimer’s dementia, but if, as is more likely in people with mild AD, you have three or four hits on the brain and remove only amyloid, then that may be too little too late. That is a more dynamic and interesting vision of AD than the old version where one arrow follows the other. I want to foster research on multiple hits at the DRI.

Q: Aren’t the leading thinkers agreeing with you already? What’s new?

A: Yes, but in many places the discussion is still too narrow. So long as we simply think Aβ42 reduction would be clinically meaningful in symptomatic Alzheimer’s, we are going to have unrealistic expectations of trials such as Expedition with solanezumab. We need to do those trials to learn, but should not hype them up as likely providing a cure. Even within amyloid alone, we need to broaden the evaluation of investigational drugs to include their effect on many more species of Aβ, not just 40 and 42 because we happen to have most experience measuring those two.

Q: What sorts of people is the DRI hiring?

A: There will be at least 400 people at the DRI, including 50 professors. Of those, at least 25 will be hired. Some will be the next generation; others will be people who are refocusing their expertise onto dementia research. We are looking for the world’s best neuroscientists, particularly those who want to shift their interest. We will bring a lot of new blood from other areas of science into dementia research. I want to be surprised.

Q: On the MRC’s website, the DRI’s ambitions cover the waterfront. What is realistic?

A: There are many stakeholders in this institute. They have many agendas. The budget is big but not big enough to cover everything in these descriptions. Recruiting me means that hard-core research is high on the agenda.

Q: What else?

A: Another urgent agenda item is better care. All the things already known to help patients—music, light, the way you interact with patients, personalized care using more personnel, fewer drugs, fewer hospitalizations. Are we really implementing these measures locally and broadly, or do we hear of them only at meetings and admire a pilot program here or there? We have a separate call for a center program around care to assess what is ready for implementation.

Q: Outside your wheelhouse?

A: I will have an associate director to help with that. I want to enhance the scientific rigor in that area. I think we can improve the quality of care research. The Alzheimer’s Society has a huge program around care, and would be a good partner for this goal of the DRI. We simply have to give better care while doing research toward a cure, so the next generation suffers less from these diseases than the current one does.

Q: Sweet irony that the U.K. appoints a foreigner to run its flagship national dementia research institute. Will Brexit make hiring harder for you?

A: I worry about that. I had second thoughts when Brexit happened. It is because I believe in the research here in the U.K. that I am still coming. I hope I can build a bridge between the U.K. and the world through dementia research. It is symbolic that MRC and the people involved in the selection chose someone from outside. They will support me in realizing my international ambitions for the DRI.

Q: A final word?

A: Post-Brexit, does the U.K. stop playing football in UEFA Champions League? If they still compete there, are they playing only with U.K. players or will they use foreign talent, like the Belgians Kevin de Bruyne and Eden Hazard? It’s the same in research. If you want to win, you need international talent.

Q: Amen to that. We thank you for this conversation.

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  1. I could not think of a better person for this position, and I'm not saying that because I want a job in London! Bart De Strooper is one of the finest scientists working in the field of Alzheimer's research. My congratulations to the selection committee.

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References

News Citations

  1. New Dementia Research Institute Announced for the U.K.
  2. New Drug Discovery Institutes to Tackle AD in the U.K.

Therapeutics Citations

  1. Solanezumab

Webinar Citations

  1. Webinar: Can ‘Cellular Phase’ Unite Disparate Data on Alzheimer’s Pathogenesis?

Paper Citations

  1. . Analysis of amyotrophic lateral sclerosis as a multistep process: a population-based modelling study. Lancet Neurol. 2014 Nov;13(11):1108-13. Epub 2014 Oct 7 PubMed.

External Citations

  1. challenge on dementia 2020
  2. Dementias Platform U.K.
  3. website

Further Reading