Testing three drugs to see if they have potential as dementia treatments

Read about a research project we funded into repurposed drugs targeting the unfolded protein response to prevent neurodegeneration in dementia.

Lead Investigator: Professor Giovanna Mallucci

  • Institution: University of Leicester
  • Grant type: Drug Discovery project grant
  • Amount: $268,634 
  • Start date: March 2015
  • End date: June 2017

What did the researchers do?

Previously Professor Mallucci and her team had identified a number of chemicals that prevented brain cells from dying in a mouse model of another neurodegenerative condition. Unfortunately these drugs were too harmful to be used effectively but did give the researchers valuable information and new areas to target with less harmful drugs.

This project built on their previous research in a mouse model of Alzheimer’s that develops changes to a protein called tau which is common in many types of dementia. Importantly this time the team looked at drugs which were already used in other conditions and so are known to be safe for people.

The team tested a range of drugs in the lab. They identified the most promising candidates and then investigated if they could stop brain cells from dying in the mouse models.

The researchers focused on two antidepressants (trazodone and venlafaxine) and a malaria prevention drug called proguanil.

What were the key results?

Unfortunately Professor Mallucci and her team found that venlafaxine and proguanil did not protect brain cells and were found to be harmful so they did not continue this area of work.

However results from Trazodone were more exciting. The team found that Trazodone stops a particular response by the cell to misfolding proteins and prevented brain cell death in the mouse model. It also protected the memory of mice and prevented the formation of tau tangles which is seen in people affected by dementia. 

The team then tested the trazodone in another mouse model of Alzheimer’s disease. In this model damage to brain cells is caused by a protein called amyloid-beta. However Trazodone wasn’t as protective in this model.

How will this help in the fight against dementia?

Overall, the team is very excited by the potential of trazodone as a new treatment for dementia. This project has identified a drug that has shown a positive effect in two models of Alzheimer’s. The results strengthen the case to test this particular drug in people and a step closer to people affected by dementia. 

What are the next steps? 

The team will need to undertake work to find the appropriate dose of trazadone and hope to begin clinical trials in people with Alzheimer’s. 

Sharing this research

The team have published their work in a number of scientific journals including:

Mallucci GR et al. RBM3 mediates structural plasticity and the protective effects of cooling in neurodegenerative disease. Nature 2015 518(7538):236-9. doi: 10.1038/nature14142 

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