Sara Imarisio, Head of Strategic Initiatives at Alzheimer’s Research UK, reveals what dementia research could deliver and how Alzheimer’s research can help us re-imagine a future in which lives are saved.
Alzheimer’s and other forms of dementia have been impacted by Covid-19. With many labs forced to close during lockdown, and social distancing measures limiting the time researchers could spend in labs, many projects in the UK were delayed or cut. Many clinical studies were delayed due to difficulty collecting data in person and many funders, including Alzheimer’s Research UK, had to reduce or pause funding for new studies to protect commitments to ongoing research.
Alzheimer’s Research UK was able to offer funding at the start of 2021 for researchers that were disproportionately affected by the pandemic, including funding early career researchers. Since then, we have reviewed applications that were put on hold in 2020. Dementia scientists are working at pace to make up for lost ground and it’s vital that they have the backing they need to regain momentum. The pandemic hit people with dementia hard, highlighting the need for treatments.
Over the last decade, dementia research in the UK has been making strides thanks to growing national and global attention, from charities, industry and governments. In the UK, the first Prime Minister’s Dementia Challenge saw government funding for research double, and in 2013 the G8 Dementia Summit culminated in global health leaders declaring an ambition to find a cure or disease-modifying treatment by 2025. Meanwhile funding from the UK’s charitable and private sector increased.
This boost in investment has been followed by an increase in the number of findings from dementia studies published worldwide. Alzheimer’s Research UK’s analysis shows that the number of publications globally increased from just 12,500 in 2010 to almost 30,000 in 2020, while an equivalent increase in capacity took place, with an estimated 160,000 scientists working on dementia research. In the UK, our 2017 Keeping Pace report estimated that the number of dementia researchers, and the number of new findings published, had doubled in six years. These developments have contributed to a view that life-changing treatments are in reach.
Despite these strides forward, dementia research has only just left the starting blocks compared to research into other major health conditions. In the UK, for example, it’s estimated that there is just one dementia researcher for every four working on cancer. So, while we must celebrate this progress, we still need to transform our level of ambition. To understand what this could achieve, we only need to look at some of the advances that have already been made.
Alzheimer’s Research UK has seen and contributed to numerous breakthroughs during this time, and the 700 dementia scientists working in the UK Dementia Research Institute – the biggest investment by the UK government in dementia research – have expectations of even more breakthroughs to come.
Another remarkable initiative is the Dementia Discovery Fund, a specialised venture capital fund investing in projects and companies that discover and develop disease-modifying therapies for dementia. It was formed by the UK government’s Department of Health and Social Care, in partnership with international pharmaceutical companies and Alzheimer’s Research UK. Thanks to this, 17 companies and projects have already been funded, with five of these projects reaching the stage of clinical trials for dementia.
New understanding of the genetic risk factors for all forms of dementia and how they affect the brain throughout life has also opened new avenues to drug discoveries. One of the most dramatic examples is the identification of TREM2 as a risk factor for Alzheimer’s and a major player in regulating neuroinflammation. From the identification of TREM2 as a risk factor, less than 10 years ago, the neuroinflammation field developed at such a speed that there are already antibodies (AL002 from Alector and AbbVie) in clinical trials targeting TREM2.
Studying neuroinflammation triggered a greater interest in the role played by microglia and astrocytes in dementia too, and greater awareness of the relevance of vascular contributions to the diseases that cause dementia. As for TREM2, there is now a growing area of research looking at the role of astrocytes and the interplay of astrocytes with other cells in the brain in regulating mechanisms that cause these diseases. A recent positive outcome from this new field of study saw the launch of AstronauTx, a UK-based biotech established from the work of the Alzheimer’s Research UK UCL Drug Discovery Institute (ARUK-UDDI). The UDDI group, led by Prof Paul Whiting, looked at ways to control the activity of astrocytes to allow neurons to function better for longer, with the aim of using this strategy as a novel approach to dementia therapeutics. This helped secure a £6.5 million investment from the Dementia Discovery Fund.
The importance of the genetic component in determining an individual’s risk of developing Alzheimer’s is an established concept. But – although a minority of Alzheimer’s cases are linked to mutations in key genes that will guarantee the development of the disease – in the majority of late-onset Alzheimer’s cases, risk is determined by a combination of lifestyle, environment and genetics. Interestingly, there is a growing body of evidence indicating that many genetic variants linked to Alzheimer’s could be found in microglia. Using iPSC lines derived from individuals with a clear and clean neuropathological assessment, and differentiating them in microglia-like cells, the UK DRI at Cardiff is creating a resource for studying diseases that cause dementia, and will eventually use this to test and develop new drugs. This new initiative, called the IPSC Platform to Model Alzheimer’s Disease Risk (IPMAR), aims to become one of the largest cellular model resources available to study Alzheimer’s, accessible to scientists worldwide.
This progress is encouraging, but there are still obstacles to overcome. One challenge is our ability to identify ways to detect the early signs of diseases that cause dementia, possibly with the support of biomarkers. A better understanding of these diseases will help to identify targets for treatments, support recruitment for clinical trials and lead to life-changing advances for people living with dementia. Future research should focus on ensuring a better stratification of patients, and consequently a more precise, effective, and personalised medicine too.
To address this issue, Alzheimer’s Research UK launched the Early Detection of Neurodegenerative Diseases, a research initiative to develop a digital tool for the early detection of diseases that cause dementia.
Another transformational area of research in the early detection and diagnosis of dementia is the study of blood biomarkers. Many studies are investigating whether this non-invasive, cheap and feasible approach could determine onset and progression of dementia, and assess people’s response to treatments. A recent paper published in Nature Ageing provided evidence of the progress being made and how the combination of different blood biomarkers could contribute to the identification and the progression of Alzheimer’s.
Recently, a number of clinical trials have failed to meet their primary endpoints of slowing the decline in memory and thinking for people with Alzheimer’s. This highlights the need for more translational research, with the aim of identifying and validating potential drug targets before they reach clinical trials. Alzheimer’s Research UK is contributing to this process with two initiatives, the Dementia Consortium and Drug Discovery Alliance (DDA). Both initiatives aim to licence drug targets that have been robustly validated.
The selection and prioritisation of targets remains a key challenge in drug discovery, with the need to reproduce and validate potential targets, guarantee their link with human diseases and understand their mechanism of action. The contribution of artificial intelligence has offered a new approach to the way molecules could be studied and proteins specifically targeted. The potential of the partnership of DeepMind’s AI program, AlphaFold, with the EMBL-EBI is unprecedented. Similarly in the dementia research field, partnerships like Exscientia with the Alzheimer’s Research UK Oxford Drug Discovery Institute (ARUK-ODDI) are a boost to the exploration of how AI could facilitate the drug discovery process. Incredible progress has been made in the past decade, thanks to a growing global focus and a groundswell of support from the public. This has given us a glimpse of what dementia research could deliver, and with the right support research will change the lives of millions.
Volume 22, Issue 4 – Fall 2021 / ELRIG Drug Discovery 2021 supplement
About the author
Sara Imarisio is the Head of Strategic Initiatives at Alzheimer’s Research UK. She manages initiatives such as the Drug Discovery Alliance, a programme that focuses on translating potential drug targets from academic research into prospective treatments. Via her role in overseeing the UK Dementia Research Institute, she catalyses collaborations amongst scientists to accelerate breakthroughs in dementia research.
