Understanding more about the changes in brain cells during frontotemporal dementia

Lead Investigator: Dr Sean Sweeney

Institution: University of York

Grant type: Project grant

Duration: 3 years

Amount: £229,413

Scientific Title: Dissecting the cellular mechanisms driving disease progression in CHMP2B activated frontotemporal dementia: Identifying innate immune activation and the co-regulation of membrane traffic in neurons

Why did we fund this project? 

Comments from members of our Research Network:

'Frontotemporal dementia is a very under-researched field and a Society priority.'

'Having seen first-hand the tragedy of two brothers suffering with frontotemporal dementia over the past few years, with no treatment available, I am delighted to read of this proposed research leading to the possibility of drugs targeted to combating…the progress of frontotemporal dementia.'

'This research could lead to an effective drug treatment for frontotemporal dementia which should make it a priority for this early onset illness.'

What do we already know?

Frontotemporal dementia is the second most common form of dementia in people under the age of 65. Detailed scientific understanding of the biology that leads to frontotemporal dementia is lacking and at present, no effective treatments are available. 

To date, researchers have identified six genes as having a role in the development offrontotemporal dementia. The researchers in this team have taken one of these genesand developed a unique genetic model of frontotemporal dementia in fruit flies (Drosophila). 

Fruit flies have been critical in recent studies of Alzheimer's disease and Parkinson's disease for uncovering crucial biological changes in the processes of these diseases and in for the identification of potential drugs. 

Many of the genes involved in human disease are the same in flies. This means that the genes that are identified are likely to be carrying out the same processes and functions in flies as they are in humans. This means that fruit fly models are a good first step in the process of understanding more about the changes within the brain that lead to frontotemporal dementia.

What does this project involve? 

The researchers will use the fruit fly genetic models of frontotemporal dementia to further develop the model and understand the changes taking place within brain cells. Using special microscope techniques, the researchers will be able to investigate changes in the biological processes within brain cells, particularly focusing on nerve cells.

They will further develop understanding of these changes, and test whether they are the same in mammals by also investigating these processes in mouse models of frontotemporal dementia, in collaboration with researchers in the United States.

How will this benefit people with dementia? 

Understanding more about the biological changes within the brain during the development of frontotemporal dementia will provide researchers with potential targets for the development of drug treatments in the future; no such drug treatments exist for this form of dementia and there are few targets already identified.

One particular target that the researchers plan to investigate already has a drug that can treat changes in it – this study may help to move this particular drug towards future trials in people.