Three key take-aways from this year’s Clinical Trials in Alzheimer’s Disease (CTAD) conference in Boston

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By Dr Susan Kohlhaas | Friday 24 November 2023

There is real optimism amongst dementia researchers. Ever since we heard the news of the first generation of Alzheimer’s drugs to pass late-stage clinical trials, there’s been a sense of momentum.

But this is only the beginning. To keep making discoveries that will move us towards a cure, we need to focus our efforts on developing treatments to tackle different aspects of Alzheimer’s disease. This will allow us to think about treating people with a combination of therapies.  At Alzheimer’s Research UK, this is what we think will be a game-changer for people with dementia.

A few weeks ago I travelled to Boston, US, to attend the Clinical Trials in Alzheimer’s Disease (CTAD) conference, where scientists from around the world gathered to share the latest results and data from clinical research. Attending conferences are one of the favourite parts of my role – there’s no better opportunity to meet people doing important work and, with the pace of discoveries constantly increasing, there’s always something new to learn.

I’d been invited to take part on a panel discussion about the future of therapies for Alzheimer’s Disease.  The panel was sponsored by Alzheimer’s Drug Discovery Foundation, one of Alzheimer’s Research UK’s closest partners, and it was a pleasure to attend and give my take on what we need to be doing as a field, as well as hear from my fellow panellists and their diverse range of views.  I think it’s fair to say we all have a lot to do, so it was good to see so many people attending and sharing their work.

In years past I might have come away with one or two key highlights from each conference, but this year I have three.  This just shows the progress we’re making as a field, and I hope people come away from this as hopeful as I am about the future of dementia research.

 

1. Breakthrough treatments could be injectable

Last year we found out that a new treatment called lecanemab could slow down cognitive decline in early Alzheimer’s disease by removing a protein called amyloid from the brain.  This was such an exciting day for us all at Alzheimer’s Research UK, because it showed for the first time that removing a protein called amyloid from the brain could slow cognitive decline. Its effects are modest at best, but that’s the case with many first-generation treatments, and our next steps will need to build on this initial success.

Among the downsides to lecanemab and other first-generation Alzheimer’s drugs is the fact that they’re currently administered by intravenous (IV) infusion every few weeks. This makes them relatively difficult to give, as IV infusions require people to visit hospitals or specialist clinics, and be treated by trained staff. Not everybody can access these services, and one of our real worries at Alzheimer’s Research UK is that the NHS simply won’t be set up to deliver these treatments, if and when they’re approved for use.

At CTAD, we heard results from a trial that had explored whether lecanemab could be given as an injection rather than an infusion.  This is a simpler method of giving the drug, and means that it could potentially be done at home.

The study showed that when given in injection form, lecanemab could lower amyloid levels in the brain as well, or better than, the infusion. There were still side effects associated with the injectable form of lecanemab, the most serious one, known as ARIA means people taking it will likely need to be monitored carefully.

It’s really great to see the field already exploring new and easier ways to offer treatments to people living with Alzheimer’s, and I look forward to seeing how this area develops into the future.

 

2. Blood tests for Alzheimer’s are showing real promise

Alzheimer’s is generally diagnosed based on people’s symptoms, such as thinking or memory problems. Shockingly, only 2% of people with a dementia diagnosis receive one through ‘gold standard’ methods, such as PET scans or lumbar punctures. Far too many people living with dementia don’t ever receive one at all. Simply put, our methods for diagnosing dementia are not scalable in the long term.

That’s bad enough in its own right, but when you think about the possibility of new treatments that will require quick and accurate diagnosis, then you can see we urgently need to improve how Alzheimer’s disease and other dementias are diagnosed.

The possibility of using blood tests as part of the diagnosis pathway has been an exciting area of research for some time. In the past few years, we’ve seen real advances in detecting proteins in the blood that build up in the brain during Alzheimer’s.  The problem is that we don’t know how accurate these tests are compared with ‘gold standard’ test such as PET scans or lumbar punctures. And we don’t quite know how best to use them in the real world.

Blood tests were a key focus of this years’ CTAD and something that many think will very soon start to change how we manage dementia. Some of the data we saw showed that some blood tests have similar accuracy to PET scans and lumbar punctures, which is really promising.

There were also some interesting discussions about how blood biomarkers could be used in the real world.  There are still some issues for the clinical community to sort, such as how accurate these types of tests need to be to be adopted into practise, how well they work in different populations or in different circumstances, and whether they could ever be used alone, or would you always need to see clinical symptoms (such as memory problems) for a diagnosis.

We’re not going to sort these questions out without big investments in research.  That’s why I’m so proud that Alzheimer’s Research UK, together with Alzheimer’s Society and the National Institute of Health Research, were recently awarded £5 million  to tackle this area thanks to funds raised by players of People’s Postcode Lottery. Our Blood Biomarker Challenge will involve working with world-class researchers to pilot the implementation of new blood tests in the NHS that can diagnose diseases that cause dementia earlier and more accurately.  Watch this space for more detail.

 

3. Next generation treatments – going beyond amyloid removal

We know that treatments for Alzheimer’s that remove amyloid protein from the brain are now on the horizon. But these treatments are modest at best and we know that there are other things happening in the brain that could be driving disease. If we’re really going to work towards a cure then we need to broaden out our treatment approaches and tackle Alzheimer’s and other types of dementia using a multi-pronged approach. At Alzheimer’s Research UK we design our research programmes to look towards where we want to be in 5, 10 or even 20 years’ time and make sure our researchers have the tools and knowledge to work on those big, game-changing things.

That’s why I’m delighted to see the field looking at new approaches to tackling Alzheimer’s Disease that go beyond amyloid removal.  At CTAD we saw some early-stage results for a potential treatment called BIIB080 that is designed to lower levels of tau. Like amyloid, tau forms clumps in the brain in people with dementia, eventually leading to damaged nerve cells and impacting a person’s memory and thinking abilities.

Although really early-stage, results presented at CTAD demonstrated that BIIB080 was able to reduce levels of tau in the brain. It also showed some signs of slowing people’s decline in memory and thinking, and was well tolerated with few side effects in people with Alzheimer’s.  This work will need to be confirmed in larger studies, but this is a very promising result and I’m looking forward to updates on this work in the years to come.

Beyond removal of proteins, it’s really important for researchers to be exploring all possible avenues to slow, stop and reverse the effects of dementia.  Early work that Alzheimer’s Research UK funded, suggested a genetic link between a cell type in the brain called microglia and dementia.  This has developed a whole new way of thinking about dementia and has led to many clinical trials that will be reporting out in the coming years.

The questions we’re asking now, about how to find ways of ensuring that brain cells are protected from changes in the brain as we age, and even thinking about mechanisms that restore lost function in the brain as diseases such as Alzheimer’s develop, are going to be incredibly important for developing next-generation treatments.  It’s only by starting to understand the complex biology of Alzheimer’s and other dementias that we’ll really start to make gains.

I’m positive that our partnerships with programmes such as our Drug Discovery Alliance, our Blood Biomarker Challenge and the incredible partnerships with organisations such as the Dementia Discovery Fund will help us to make these much-needed gains.

I came away from CTAD heartened to see progress in so many areas that are important to people like me, who have seen the devastation that dementia can cause.  But I also come away knowing that we as a field have a lot of work to do, if we’re to really move towards a cure at the pace and scale that people with dementia and their families deserve. At Alzheimer’s Research UK, we’re incredibly grateful to each of our supporters for making the work we do possible.

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About the author

Dr Susan Kohlhaas

Dr Susan Kohlhaas is the Director of Research at Alzheimer’s Research UK where she currently drives the research agenda.

Susan has over a decade of experience at medical research charities, most recently as Executive Director of Research and External Affairs at MS Society.

Dr-Susan-Kohlhaas