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Alzheimer’s disease: Fighting back against a growing threat

Published on 11/09/17 at 11:09am

September marks Alzheimer’s Awareness Month, a crucial calendar period as the global threat of the disease slowly grows. To mark the occasion, Pharmafocus spoke to experts at two of the UK’s most foremost institutions devoted to Alzheimer’s research.

Carol Routledge, Director of Research at Alzheimer’s Research

What message would you like to share during this month?

The first point is, of course, about awareness. I do think there are still misconceptions around dementia. I think some people still think that it is just ageing but it’s really important to say that dementia is a set of underlying symptoms which are a number of different, complex diseases. Age is a risk factor – one of the greatest risk factors – but dementia is not ageing.

The other point is a plea, of sorts. There has been significant funding and investment in dementia research, particularly following on from the G8 dementia summit discussions, which is great. However, it is just the beginning; if there is a feeling that investment in dementia research is done, it really isn’t. For instance, if you think of funding into cancer research and think of where they were 30 years ago, the money continued to be devoted to area. They didn’t think: ‘We’ve put this money into cancer research, let’s stop and think of something else’. This is why we’re consistently seeing developments in the cancer area and that’s what we need to see in dementia.

What recent developments are giving clinicians and patients hope?

There are a few key areas that are starting to look a lot more promising. One of those areas is neuroinflammation. Genetic risk factors have pushed researchers in that direction and previous research in the field has been slightly blunt up until now; we’ve just looked for agonists and antagonists, I think research is developing to be more subtle than that. Some of the targets that are coming through are regarding subtle modulation of neuroinflammation, and the reason that is important is that the process actually changes as the disease progresses. If you look at neuroinflammatory targets and completely block them, the chances are you may exacerbate the disease at certain stages, even if you think you are benefitting the disease at a later stage. We need to understand the subtleties around some of those targets and how we can normalise the functions rather than completely block or completely stimulate something. In both academia and pharma research, this is a process that is certainly beginning to happen.

The pharma industry can often be seen as being driven by commercial outcomes, where do industry and charity aims dovetail?

We know pharma has to be commercial, one of the reasons is so that it can put that money back into research; if we didn’t have pharma partners, charities couldn’t fund Phase 2b and Phase 3 studies. We rely strongly on our collaborations with pharma research, especially in some of our strategic initiatives, like the Drug Discovery Alliance. The kind of help that we get from pharma partners, in terms of formulating project plans and pulling apart issues to understand how we best move forward from those, has been brilliant.

I know it benefits them as well, as they will see very good projects moving from the early research space to drug discovery. More than that, they genuinely want to see some of these ideas work and come forward. When I was in pharma, I was interested in getting good molecules put forward and, for most researchers, you’re not thinking about commercial targets, you’re thinking about moving your project forward into the clinic.

What do the short and long-term prospects look like in developing new therapies for Alzheimer’s?

I don’t think there are going to be any blockbusters or any ‘eureka’ moments in the near future. As a disease on its own, Alzheimer’s is so heterogeneous that there will be many sub-populations of patients within this area and I think that understanding this is of key importance. This brings me to a major point: if we can better diagnose patient sub-populations then we can better target treatments. The disease starts 20 to 30 years before we begin to see noticeable symptoms and the signs are usually mild memory loss, but that is too far down the line of the disease. If we can bring diagnosis 10 to 15 years earlier, maybe some of the treatments that have failed in the clinic recently might not fail this time.

Doug Brown, Director of Research and Development at the Alzheimer’s Society

The prevalence of Alzheimer’s is rising steadily with ageing populations across the world. How can we work to combat this?

There are 850,000 people with dementia in the UK at the moment and 44 million worldwide, and because we’re all living longer, the numbers are increasing significantly. We need more research to try and bring through breakthroughs in prevention, treatment and cure, and we’re making a huge amount of progress on that. What we also need to do is to tackle the social care challenges that come with that, particularly in low-to-middle income countries where dementia is a bigger issue due to their age demographic and how those populations are ageing. Alongside the research efforts that we are leading, we’re also working through bodies such as the World Dementia Council and Alzheimer’s Disease International to make the disease a global priority. We’ve made significant progress in just the last few months on this, where the World Health Assembly voted to treat dementia as a priority. This triggered the World Health Organization to develop a global action plan which will come up with some clear goals for all member countries to create change for people affected by dementia.

What recent trends and developments are helping to turn the tide against this devastating disease?

We’re seeing big collaborative efforts – for example, data sharing platforms such as Dementia Platform UK – which is fantastic because researchers are coming together to share their cohort data. This gives us much more power when we want to look into that data to spot patterns and trends, which tell us about the causes and risks of the disease.

We’ve also seen new tools developed, which has been really helpful when looking at the main proteins – amyloid and tau – related to Alzheimer’s disease in the brain. This is how we are changing the way clinical studies are being done because if we can look at those molecular changes in more detail, it allows us to have a much better understanding of the underlying disease. This provides a useful platform for other research and treatment development to drive that forward.

The third one is the shift towards performing clinical trials at an earlier stage in the disease process. There was a discovery published a few years ago which showed that the changes in the brain start happening between 10 and 15 years before someone experiences their first clinical symptom of dementia. This research has had a significant impact on how we do clinical trials, and we’re now seeing them in the very early stages, if not prodromal stages, of Alzheimer’s and other forms of dementia to give us the best chance of identifying a disease-modifying effect.

There are now six times as many researchers working in cancer than in dementia. What does this mean for the field and how can it be tackled?

This is a real issue for the dementia research field – we just don’t have the right-sized workforce in the UK. There’s still this issue in other countries, but being a UK research funder, it’s our priority to tackle this. We know from cancer that through research, the right investment, and having the right number of people working, we can develop preventions, treatments and cures. We would want to see exactly the same progress for dementia and those affected by the condition. We’re leading the way in building that research capacity and capability in the UK; we have a dementia research leaders programme that’s absolutely focused on early-to-mid career researchers, looking to attract, but also retain, the very best brains in dementia research. We want to build on this success so we can bridge that gap and see the same level of progress that we’ve seen in cancer research.

In terms of lifestyle changes, what steps can be taken to minimise risk?

Generally, what is good for your heart is good for your head. It’s the cardiovascular risk factors and lifestyle changes that we can all make which will give us the best chance of reducing our risk of developing dementia in later life. So a healthy diet, possibly following the Mediterranean diet of oily fish and green vegetables. Exercise on a regular basis is good. Not smoking. And even perhaps the odd glass of red wine – a glass, not a bottle – can look to potentially reduce our risk. The key message is here is that it’s never too late to make these changes, even following a diagnosis of dementia. This is good advice that will have a positive impact, not just in reducing risk but in improving quality of life following a diagnosis.

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