Alzheimer’s Research UK starts AI-based drug hunt with Exscientia

Medical charity Alzheimer’s Research UK has teamed up with artificial intelligence specialist Exscientia to find new drug treatments for the devastating neurodegenerative disease. 

The alliance will see Exscientia work with the charity’s Oxford Drug Discovery Institute (ODDI) to find therapeutics that target the neuroinflammation associated with Alzheimer’s disease (AD), focusing in particular on the NLRP3 inflammasome pathway.

Inflammasomes are a group of intracellular proteins associated with the inflammatory response, and prior research has linked the NLRP3 inflammasome to the aggregation of amyloid beta and tau protein – which together form the characteristic plaques and tangles in the brains of AD patients.

One recent study has pointed to NLRP3 as a potential a link between amyloid and tau disruption, so drugs inhibiting it may be able to address two AD pathologies in one molecule.

“Activation of the NLRP3 inflammasome has been shown to have an important role in AD pathogenesis,” said the two groups in a joint statement.

“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.”

UK biotech Exscientia has signed a string of partnerships with pharma companies and other research-based organisations to apply its AI-based drug discovery platform.

The company hit the headlines last year when one partner – Japan’s Sumitomo Pharma – started clinical trials of a drug candidate for obsessive compulsive disorder, said to be the first medicine developed using AI to enter testing in humans.

It reckons its use of AI and machine learning can trim years off the current 12- to 15-year cycle from early research to marketed product.

The project with the ODDI will draw on research conducted over years by the Oxford group on the NLRP3 pathway, with its biology and screening expertise fed into Exscientia’s Centaur Chemist AI-powered drug design platform.

Dr John Davis, chief scientific officer of ODDI, said that the Exscientia partnership “will enable us to investigate multiple molecules in parallel and accelerate the project towards candidate declaration”.

He added: “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.”

NLRP3 inflammasomes have emerged as something of a hot target in the biopharma sector over the last couple of years. Last September, Roche paid €380 million (around $460 million) to buy Inflazome and its pipeline of oral NLRP3 drugs, which are being developed for Parkinson’s disease, AD and peripheral inflammatory disorders like gout.

In 2019, Novartis also bought into the category via a $310 million takeover of IFM Therapeutics, which is developing NLRP3 drugs for atherosclerosis and non-alcoholic steatohepatitis (NASH), while UK startup NodThera raised $55 million last year for its own NLRP3 programme, eyeing NASH and diabetes.

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