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Manchester Institute for Collaborative Research on Ageing

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Identifying a New Drug Target for the Treatment of Alzheimer's Disease

This is a PhD project funded by the Alzheimer’s Society to develop new small molecule inhibitors of inflammation that could be used to treat dementia.

Inflammation, part of our body’s immune response, increases as we age and is known to contribute to diseases of ageing such as Alzheimer’s disease. Specifically, an inflammatory complex inside cells called the NLRP3 inflammasome is known to drive a particularly damaging form of inflammation.

We had previously reported that fenamate NSAIDs could inhibit NLRP3, opening the possibility of a drug repurposing strategy. However, NSAIDs have side effects and so the challenge of this project was to develop new and more potent inhibitors of NLRP3 whilst avoiding any of the side effects associated with NSAIDs.

Tessa Swanton is the PhD student working on the project and has developed a new class of NLRP3 inhibitor that avoids any of the non-specific off target effects associated with NSAID use. We are now further developing and characterising these molecules.

This has been an exciting and challenging project that led to a new class of inhibitor that targets a new mechanism of action

Professor David Brough

Working alongside a diverse team of talented scientists is what has made this project so great.

Tessa Swanton

Project Objectives

  1. To deliver new insights into the regulation of the NLRP3 inflammasome
  2. To develop new small molecule inhibitors of the NLRP3 inflammasome

Principle Investigator

  • Professor David Brough, University of Manchester

Manchester Co- Investigators

  • Dr Catherine Lawrence, Dr Sally Freeman

Additional Universities/External Partners

  • University of Oxford

Funding period

  • September 2017 – September 2020

Disciplines involved

  • Chemistry
  • biology

PhD Students

  • Tessa Swainton
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