Scientists Rise To Challenge To Untangle Key Dementia Protein

Researchers at four UK universities have been awarded up to £100,000 each in a bid to solve one of the biggest challenges in dementia research, with the goal of helping the early stages of drug development. Scientists in Birmingham, Cambridge, London and Manchester will use stem cells to develop a model of tau – a key protein that builds in the brain during both Alzheimer’s disease and frontotemporal dementia (FTD) – as part of the CRACK IT Challenges programme.

Led by the UK’s National Centre for the Replacement, Refinement and Reduction of Animals in Research (NC3Rs), the competition sets out a series of scientific challenges, which scientists are asked to achieve using methods that help replace or reduce the number of animals in research, or which improve animal welfare. For its UnTangle challenge, the NC3Rs has partnered with Alzheimer’s Research UK to fund research aimed at advancing treatments that target tau – a protein that tangles inside brain cells as Alzheimer’s and FTD develop.

Four UK research groups will compete on the first phase of development, working to create a network of brain cells in the lab using human stem cells. Stem cells can be turned into any other cell type in the body, allowing scientist to mimic these cells in the lab. The four groups will be challenged with developing brain cells that suffer damage from tau, which can then be used to test the effects of compounds aimed at stopping this damage. Such a model could be used in early drug development to identify how effective potential new compounds may be, as well as highlighting any unexpected effects.

CRACK IT’s staggered funding approach enables applicants to look at higher-risk, more innovative technologies. Phase 1 finalists will have six months to develop the proof-of-concept studies, with the most successful group winning a three-year contract of up to £1m for further development in phase 2.

Sponsored by Alzheimer’s Research UK, Lilly and Janssen, the following phase 1 contracts have been awarded:

  1. Dr Eric Hill, Aston University: £95,453
  2. Professor Maria Grazia Spillantini, University of Cambridge: £66,898
  3. Dr Selina Wray, University College London: £99,956
  4. Dr Christopher Ward, University of Manchester: £81,956

Dr Eric Karran, Director of Research at Alzheimer’s Research UK, said:
“We are delighted to be supporting this CRACK IT Challenge, and look forward to seeing the early results from our Phase 1 finalists in a few months’ time. The tau protein is known to be involved in several neurodegenerative diseases, including Alzheimer’s disease and frontotemporal dementia. We hope that compounds to target this protein could hold potential to treat these diseases, but in order to develop such a compound it’s crucial to have robust test systems with which to measure the effects of potential drugs accurately. The task these researchers are taking on is not an easy one, but this work could have important implications for the development of much-needed new treatments for these diseases.”

Funding for the 2014 CRACK IT Challenges scheme has come from the Technology Strategy Board’s Small Business Research Initiative (SBRI).

Stephen Browning, the Technology Strategy Board’s Head of SBRI & SMART said:
“It’s great to see the NC3Rs expanding the use of SBRI as part of the CRACK IT programme to enable SMEs and start-ups coming from universities to develop new and innovative technology solutions to reduce the need for animals in research and testing.”

Dr Vicky Robinson, Chief Executive of the NC3Rs said:
“In many cases drug-induced toxicity results in a significant number of new drugs failing before they reach the market place; often this is not identified until animal studies have taken place. By developing more predictive technologies and approaches for use in the earliest stages of drug development, industry scientists will be better equipped to identify whether a new drug is suitable for later-stage testing in animal studies and humans. This is not only more cost-effective, but has the potential to significantly reduce the number of animals needed overall.”















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