Neuroinflammation collaboration targeting inflammasome steps-up-the-pace in race for Alzheimer’s disease medicines that alleviate the burden of devastating disease
Oxford: Exscientia, a leading AI Drug Discovery company, has today announced its collaboration with the Alzheimer’s Research UK University of Oxford Drug Discovery Institute (ARUK-ODDI) to develop medicines targeting neuroinflammation for the treatment of Alzheimer’s disease (AD).
AD is the most common form of dementia worldwide, with an estimated 44 million people living with AD or related form of dementia [1,2]. Symptoms of this progressive disease are debilitating, distressing – for both those with the disease and their loved ones –and there is currently no cure .
This exciting new partnership unites Exscientia’s AI-driven molecular design capabilities with the deep therapy area knowledge and technical expertise of the ARUK-ODDI.
The collaboration will focus on a specific neuroinflammatory pathway implicated in the development of AD. Activation of the NLRP3 inflammasome has been shown to have an important role in AD pathogenesis and, while there have been other efforts to develop anti-inflammatory drugs for AD , targeting NLRP3 inflammasome inhibition in the brain is an innovative therapeutic approach.
Exscientia’s proven AI-driven technology will be applied to efficiently generate high-value novel clinical assets targeting this pathway. Feeding into this are chemical starting points that modulate NLRP3 inflammasome formation identified over years of research by the ARUK-ODDI. Coupling Exscientia’s Centaur Chemist® AI-design systems with the ARUK-ODDI’s biology and screening expertise is expected to speed up delivery of distinct candidate molecules for AD.
Exscientia’s COO David Hallett commented: “Alzheimer’s is a dreadful disease that affects tens of millions worldwide. Despite clinical trials of numerous agents over a wide range of mechanisms, the last new Alzheimer’s medication, was approved nearly two decades ago. Alzheimer’s drug development is costly, complex and extremely challenging with clinical trial failure rate being the highest of any therapeutic area. Our mission is to make novel drugs available to all and we are excited to utilise our AI drug discovery platform and work alongside the expertise of the Alzheimer’s Research UK-Oxford Drug Discovery Institute team to accelerate innovation and develop potential medicines to solve this global epidemic.”
Expanding on this new relationship, Dr John Davis, CSO of the Alzheimer’s Research UK-Oxford Drug Discovery Institute drew attention to the benefits gained from the complementary capabilities of both partners: “We are delighted to be partnering with Exscientia. Their state-of-the-art AI capabilities will enable us to investigate multiple molecules in parallel and accelerate the project towards candidate declaration. Human genetic variation points towards a critical role for the body’s immune system in an individual’s risk of developing Alzheimer’s disease. It is vital that we develop treatments that target neuroinflammatory mechanisms underlying dementia.”
Dr Sara Imarisio, Head of Research at Alzheimer’s Research UK said:
“Scientist’s at our ARUK-Oxford Drug Discovery Institute are ideally placed to capitalise on the latest discoveries and work with partners to help translate this into drugs that could be tested in clinical trials. With nearly one million people in the UK living with dementia, there isn’t a moment to waste.”
REFERENCES: World Health Organization. Fact Sheet. Dementia. https://www.who.int/news-room/fact-sheets/detail/dementia#:~:text=Alzheimer’s%20disease%20is%20the%20most,dependency%20among%20older%20people%20worldwide  Alzheimer’s News Today. https://alzheimersnewstoday.com/alzheimers-disease-statistics  NHS. Alzheimer’s Disease. https://www.nhs.uk/conditions/alzheimers-disease  Immunity’s flipside: Microglia promote Alzheimer’s pathology during inflammation. https://www.novusbio.com/antibody-news/immunitys-flipside-microglia-promote-alzheimers-pathology-during-inflammation
Notes to Editors:
About the NLRP3 inflammasome in the pathophysiology of Alzheimer’s disease (AD)
Inflammasomes are part of the innate immune system and are responsible for a wide range of inflammatory responses. In AD, activated NLRP3 inflammasome leads to the release of pro-inflammatory cytokine (IL-1 beta) and ASC (apoptosis-associated speck-like protein containing a caspase-recruitment domain) speck into the intercellular space. The release of ASC specks from microglia promotes amyloid-beta aggregation in AD. The accumulation of amyloid-beta in plaques, aggregation of hyperphosphorylated tau in neurofibrillary tangles and neuroinflammation, together result in neurodegeneration and cognitive decline that characterize AD.
Exscientia is an Artificial Intelligence (AI)-driven pharmatech, committed to discovering medicines in the fastest and most effective manner for patients. As a clinical stage company, Exscientia is the first to progress AI-designed small molecules into a clinical setting, demonstrating the ability of AI to transform the pharmaceutical industry.
Drug design is precision engineering at the molecular scale. To transform the industry, Exscientia has built dedicated AI systems that efficiently learn from the widest range of data and consistently re-apply enhanced knowledge through iterations of design. Because Exscientia’s AI systems learn more rapidly and effectively than human-led efforts, candidate molecules satisfying complex therapeutic requirements are discovered with revolutionary efficiency.
Exscientia puts AI at the centre of its strategy to revolutionise drug discovery, designing therapeutics for areas of high unmet need, that will positively impact patients.
About Centaur Chemist®
Centaur Chemist® is Exscientia’s solution to AI-driven drug design combining the latest AI-tech with the therapeutic experience of seasoned drug hunters. Driven by algorithms that mimic evolutionary design as well as deep learning to analyse complex information and active learning to extract insights from sparse, high-value datasets, Centaur Chemist® has been skilfully engineered to work with widest range of discovery data to ensure application to the widest range of discovery projects.
Centaur Biologist® supports the discovery and prioritisation of drug targets, ensuring that any candidate molecules developed will be aligned with key therapeutic objectives. With deep learning and vector embedding techniques Centaur Biologist® pinpoints trends and insights from big data and captures semantics that predict new unexpected associations.
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About the ARUK-Oxford Drug Discovery Institute, University of Oxford
The Alzheimer’s Research UK Oxford Drug Discovery Institute is a drug discovery team, founded with funding from the charity Alzheimer’s Research UK, with the objective of accelerating the translation of basic science generated within universities towards therapeutic utility. The focus of the team is upon discovering treatments for the neurodegenerative diseases underlying dementia. Although Alzheimer’s disease is the most common cause of dementia and the charity bears its name, the remit of the ARUK-ODDI covers all diseases and mechanisms implicated in the different neurodegenerative diseases that contribute to dementia, including Alzheimer’s disease, Parkinson’s disease, vascular dementia and frontotemporal dementia. For more information, visit https://oxford-ddi.alzheimersresearchuk.org/about-the-institute/.
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