Understanding the role of key genes in frontotemporal dementia

Lead researcher: Dr Kurt De Vos

Institution: University of Sheffield

Grant type: Project

Duration: 3 years

Amount: £183,251

Scientific title: Role of TMEM106B in C9ORF72-related frontotemporal lobar degeneration

Why did we fund this project?

Comments from the Research Network:

'Previous research has provided clues to build on for frontotemporal lobar degeneration. It will also look at existing drugs for Parkinson's, Huntington's and motor neurone disease in their disease models.''

'FTLD is devastating as it affects such young people... a treatment on this area could lead to [finding treatments for] other types of dementia.'

'Aims to identify faults caused by faulty genes and thereby facilitate the development of appropriate drug treatments.'

What do we already know?

Frontotemporal lobar degeneration is the name given to the loss of nerve cells in the frontal and temporal lobes of the brain, causing a form of dementia called frontotemporal dementia. Frontotemporal dementia often affects people under the age of 65. The causes of nerve cell loss in this condition are known to be related to the build-up of abnormal clumps of proteins, but the mechanisms behind this are not well understood.

Protein clumping is actually a common occurrence in our cells. However, these clumps are usually broken down by the cell in a process called autophagy. The researchers behind this project therefore aim to investigate whether it is a failure in autophagy that causes the build-up of clumps in nerve cells affected by frontotemporal dementia. This theory is supported by the fact that two key genes known to increase the risk of frontotemporal dementia - called C9orf72 and TMEM106B - are involved in autophagy.

What does this project involve?

The researchers will use cells grown in the lab, including nerve cells, to more fully understand the role of the TMEM106B and C9orf72 genes in autophagy. They will also investigate whether these genes contribute towards the nerve cell loss seen in frontotemporal dementia. They will adjust the levels of these genes and see how this affects the function of the cells, particularly focusing on autophagy. The researchers also aim to understand whether there is any link between TMEM106B and C9of72 in affecting the process of autophagy and in the development of frontotemporal dementia. 

How will this benefit people affected by dementia?

Understanding the roles that faulty genes play in disease mechanisms is an essential part of finding suitable targets for potential treatments. The researchers hope that if they can show that autophagy is not working properly in frontotemporal dementia then the search can begin for drugs that correct this fault. As other forms of dementia are also caused by clumps of proteins, this project could also help in our understanding of whether autophagy also plays a role in these conditions.

There are currently no treatments available for frontotemporal dementia, so this project will help to improve our understanding of the disease process and could help in the development of future treatments.