Neurology Central

Finding the answers for Alzheimer’s disease: Alzheimer’s Research UK profile

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Neurology Central talks to Dr Emma O’Brien, Science Communications Officer at Alzheimer’s Research UK (ARUK) about the history of the charity, current projects and how they hope to contribute to improvements in diagnosis, prevention and treatments for Alzheimer’s Disease.

Why was ARUK created and what are the aims of the charity?

ARUK was founded in 1992 – it was originally called the Alzheimer’s Research Trust and the mission was to defeat dementia through research. At the time there wasn’t any investment into the biological basis of Alzheimer’s and there was no coherent, focused attempt to try and find treatments.

In 1997 we established the ARUK Research Network, which now consists of 15 Centres across the UK and over 1000 researchers, with the aim of bringing together dementia researchers from lots of different disciplines to collaborate. The Research Network funds primary projects by providing small injections of cash to help teams collect pilot data that can then be used in applications for larger grants. It also provides equipment grants and networking opportunities to bring individuals from across each Network Centre together to share their resources, expertise and to forge new collaborations.

It wasn’t until 1998 that our first Major Project was funded. This went to a researcher at the University of Cambridge (UK) who was investigating why nerve cells become damaged in Alzheimer’s disease; the study really laid the foundations for other work in that area.

ARUK funds biomedical research that takes us closer to improving diagnosis of dementia, preventing dementia, but ultimately finding treatments that will tackle the diseases that cause dementia. This includes looking at ways to halt nerve cell death or clear toxic proteins to ultimately find disease-modifying treatments.

 Can you tell us a bit about the ARUK Drug Discovery Institutes?

People with dementia are at the heart of what we do, so all the research we fund must have a translational potential. That’s the reason why, now that we’ve grown significantly as a charity, this February we launched our network of Drug Discovery Institutes. There are three Drug Discovery Institutes, located at the University of Oxford (UK), the University of Cambridge (UK) and at University College London (UK). These have been created to try and get promising discoveries from academic laboratories into a state where they can be targeted with drugs. For this early phase drug development, each Drug Discovery Institute will have a different focus, looking at different types of targets, and using a range of different parallel approaches to help reach a treatment sooner. We’re really trying to engage researchers from across the country who are active in this field to approach the Drug Discovery Institutes with targets for drugs that they think could be worth looking at and pursuing.

How does this work fit in with drug development taking place in the pharmaceutical industry?

In the last few years we’ve launched the Dementia Consortium, which is a partnership between ourselves, the Medical Research Council (MRC) Technology (a technology transfer expert) and the pharmaceutical companies Eisai and Lilly. The aim of the Dementia Consortium is to fund robust target validation and early stage drug discovery. Having the pharmaceutical companies involved is beneficial because they have resources, and consequently expertise, that academics don’t always have. They may be able to provide tool compounds or give advice on attempts that have already failed.

So far we’ve funded two studies through the scheme, one that is taking place in Italy and was funded entirely by ARUK, and another, in Southampton, which one of the pharmaceutical companies decided to invest in, looking at the role of the immune system in Alzheimer’s.

A lot of people are slightly wary of the involvement of pharmaceutical companies in publicly funded research, but it is important to realize that finding a drug for Alzheimer’s disease or the other causes of dementia is a hugely costly process. At some point pharmaceutical companies will be needed in order to fund clinical trials, especially in the Phase III stage, and to ultimately get things on the market.

In our new Drug Discovery Institutes where we’re aiming to build the drug development expertise of academics, researchers will be working with biotechnology companies and small pharmaceutical companies to build this knowledge. Working with the pharmaceutical industry is going to become increasingly important in order to make sure that new treatments can actually make the translation into people.

What areas of research do the projects you’re currently funding focus on?

We fund a very broad range of topics – from experiments in cells in the lab that seek to dissect the molecular chain of events that leads to disease, all the way up to clinical trials in people. Through the Dementia Consortium we’ve recently funded a project at the University of Southampton (UK), investigating the role the immune system plays in the initiation and progression of Alzheimer’s disease [1]. A previous genetic study [2] indicated that a gene termed TREM2, which is involved in the brain’s immune system regulation, can increase the risk of Alzheimer’s disease when mutated. This ignited a field of research trying to understand how the immune system’s involved in the disease and other causes of dementia, and whether we can dampen or harness the immune system in order to be able to treat the disease. The University of Southampton project is looking at regulating one component of the brain’s immune system and trying to find ways to dampen the brain’s immune response in the hope that this will help to protect nerve cells. This is based on the thinking that although the immune system theoretically should be protecting us, perhaps it’s a bit too much of a good thing and there’s collateral damage with the immune response that may lead to nerve cell death.

We’re funding several projects that aim to improve diagnosis. This includes work at Imperial College London (UK) [3], using PET scans to monitor the inflammatory response to damage in the brain in people with Alzheimer’s disease. This will provide information to work out whether it may be possible to use this to monitor the progression of the disease and perhaps response to therapy in the future.

It’s also important to understand how changes in the brain relate to lifestyle. We’ve recently invested in a large MRI study that is being carried out at University College London, in conjunction with the Medical Research Council’s 1946 birth cohort project. The aim is to explore the relationship between changes that have occurred in an individual’s brain and what we know about their life history. This will hopefully reveal a lot about how lifestyle impacts brain function. The team will also be following the cohort to see any individuals develop dementia.

You can read more about our Research Strategy and the projects we fund here

Do you currently have any studies focussing on Alzheimer’s prevention?

We held a workshop earlier in the year to convene prevention experts to discuss opportunities and barriers in prevention research – where can research funding be best invested: is it on looking for new risk factors or is it on homing in on what we already know and working out how best to advise people to reduce their risk?

We are currently funding projects exploring the link between blood pressure and brain changes. At the University of Bristol [4] a research team are examining the brain tissue of individual’s known to have lived with high blood pressure in order try and tease apart the biological links between blood pressure, the build-up of toxic proteins in the brain and consequently nerve cell death.

A study at King’s College London [5] is also just starting, concentrating on the links between stress and changes in systemic blood, and interference with the brain.

In terms of risk factors for dementia, one of our biggest impacts as a charity has been in the field of genetics. ARUK funding has helped in the discovery of 20 out of the 21 known risk genes for Alzheimer’s. I think we’ll keep seeing the fruits of this research for years to come and I think it will ultimately translate into therapeutics – by understanding the pathways of the disease through genetics we’ll hopefully be able to actually target them.

What is your stance on recent claims that dementia rates are actually reducing?

While the study suggests that dementia prevalence might be stabilizing, the numbers of individuals with dementia are unlikely to fall because we’re all living longer, and age is the biggest risk factor for the disease. However, interestingly the study did indicate that public messaging around cardiovascular health seems to have had an impact on dementia numbers; because what’s good for your heart is generally good for your head.

Increased awareness around cardiovascular health may have impacted on dementia risk, but this will probably fluctuate depending on the prevailing health issues in different generations. For example, now there are worrying statistics about diabetes and obesity in midlife, which could impact on health in later life.

Current evidence suggests that maybe one-third of dementia might be preventable, but we don’t know what the cause is and that’s why it is important to keep understanding the pathways and trying to come up with treatments. There will always be a need for treatments for dementia.

What kind of impact does your research have on care practices for dementia patients?

As we were set up to fund biomedical research, that is our main focus, however care and the role of caregivers is obviously a very important aspect of dementia. This year an ARUK project in Cambridge [6] commenced to try and identify whether oxytocin could help treat behavioral symptoms and traits such as lack of empathy in individual’s with fronto-temporal dementia . There was a big stress on the positive impact this would have on caregivers, so although we don’t directly fund research into care, caregivers are at the forefront of researchers’ minds.

What is your process for deciding who receives funding for projects?

We have a Grant Review Board that is made up of over 15 dementia research experts from across the spectrum of research, from basic biologists to clinicians and imaging experts. We have two rounds of grant deadlines a year for most of our projects, including Clinical Research Fellowships and Preparatory Clinical Research Fellowships. Initially, grant applications are sent out to external review to establish whether they are within the remit, if it is ‘good science’ and if it is something that could truly help people with dementia. After any applications that don’t meet the initial criteria have been rejected, the remaining proposals are sent to the Grant Review Board where recommended projects for funding are decided.

We’ve also recently introduced a patient involvement aspect, meaning any grants that involve people are sent out to a lay reviewer to decide if it is feasible for an individual with the specific form of dementia being investigated to actually take part in the proposed study.

The process takes approximately 6 months from application to final decision, but it enables us to ensure we’re funding the best work, and investing the money that has been so generously donated, into great projects. We want to fund good science and we want to fund research that has a translational potential. What we’re looking for is a good coherent proposal from a researcher and a team that have the expertise to achieve the aims set out.

Are many of the projects at the clinical trial stage?

We do want to fund clinical trials, however it would have to be Phase I and Phase II clinical trials because Phase III would be far beyond what we could fund at the moment. We have a relatively new Global Clinical Trials Fund for which the application deadline is in January, so hopefully we’ll get fund some good projects through that.

We do find a lot of clinical research, for example studies using brain scans, patient samples and cognitive tests. At the moment approximately one-third of our research projects involve animals so by no means is animal research the largest proportion of what we fund.

What impact do you hope ARUK research will have over the next 10 years?

We want to invest as much money as we can in finding treatments for not only Alzheimer’s but the other causes of dementia. Through the establishment of our Drug Discovery Institutes we hope to bridge the gap between researchers who are working in the laboratory to a drug in clinical use.

For many years we’ve been funding basic biology, genetic studies and research into cellular pathways that help us to understand how the brain works, so I feel confident that we can build on these foundations. We’ve now got the money to be able invest in larger and more strategic projects – like our Drug Discovery Institutes – to make sure that treatments are developed, so I hope in the next 10 years we’ll really see the translation of all this basic biology into something that could be used in the clinic.

We’ve had the UK Prime Minister’s challenge on dementia and both the media and the public are talking about dementia more. Now is the time to galvanize upon that and use public support to lobby government to make sure they keep dementia at the top of the political agenda.

Governments need to increase their funding and we need to encourage more researchers into dementia research – at the moment cancer researchers outnumber dementia researchers in the UK at a factor of 6 to 1. We also need to encourage more clinicians to get involved and to use their expertise to progress the field.

We’re optimistic. Obviously science is never easy, but I think by trying lots of different approaches, we will find the answers to this huge medical challenge.

For more information on funding opportunities from ARUK click here

References:

  1. www.dementiablog.org/the-dementia-consortium/
  2. Guerreiro R, Wojtas A, Bras J et al. TREM2 variants in Alzheimer’s disease. N Engl J Med. 368(2), 117–127 (2013).
  3. www.alzheimersresearchuk.org/research-projects/imaging-inflammation-brain-people-memory-problems/
  4. www.bristol.ac.uk/clinical-sciences/people/seth-love/index.html
  5. www.researchgate.net/profile/Richard_Killick
  6. www.alzheimersresearchuk.org/cambridge-trial-to-explore-effects-of-hormone-on-frontotemporal-dementia/

The opinions expressed in this interview are those of the interviewee and do not necessarily reflect the views of Neurology Central or Future Science Group

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