Lead Investigator: Professor Giovanna Mallucci
Institution: University of Cambridge
Grant type: Drug Discovery project grant
Duration: 24 months
Amount: $268,634 (this project amount is in dollars as it was awarded as part of a joint funding call with the Alzheimer's Drug Discovery Foundation - Alzheimer's Society is funding half of this amount)
Scientific Title: Repurposed drugs targeting the unfolded protein response to prevent neurodegeneration in dementia.
What do we already know?
Previous work by Professor Mallucci and her team identified chemicals that stopped brain cells from dying in a mouse model of prion disease. Prion disease leads to the death of brain cells as a result of proteins that aren't 'folded' correctly, causing them to not work.
These misfolded proteins, or prions, spread throughout the brain causing harm to brain cells leading to their death. This chemicals used by the researchers didn't stop these faulty proteins from forming, but did protect the cells and stop them from dying.
The death of brain cells is the cause of symptoms and progression that we see in dementia, so it's possible that the same sort of method could be used to prevent cell death in other diseases too, including Alzheimer's disease and other forms of dementia.
An additional challenge is posed as the chemicals that the researchers used to save the brain cells in their previous model were too harmful to be used as an effective treatment. However, looking at how those chemicals worked did give the researchers valuable information and new areas to target with less harmful drugs.
What does this project involve?
This project will develop the researchers' previous research in mouse models that produce changes similar to those seen in Alzheimer's disease and changes to a protein called tau, seen in many types of dementia. As part of our Drug Discovery programme, the researchers will test drugs that currently exist for other conditions.
In their work to find drugs that work in a similar way to their previous work, but without the harmful side effects, the research team have tested a range of drugs in the lab. They will now test the most promising of these to see if they stop brain cells from dying in mouse models of dementia.
It is hoped that these drugs have similar beneficial effects to those seen in the researchers' earlier work. If this is the case, work can then be undertaken to find the right dose and take the drugs into clinical trials with people with dementia.
How will this benefit people with dementia?
There are currently limited treatments for Alzheimer's disease, and none for other forms of dementia. We need to find better treatments for the condition. However, it can take up to 20 years to develop a drug from scratch.
Our Drug Discovery programme aims to take drugs that are already used for other conditions and 'repurpose'them for the treatment of different forms of dementia. This could greatly speed up the time that it takes to get a new treatment to people with dementia.
This study will test drugs to see if they look promising, and could be taken forward into clinical trials in people with dementia, moving us closer to potential new treatments.