Investigating a potential target for treatment of frontotemporal dementia

Lead Investigator: Dr Christopher Miller

Institution: Institute of Psychiatry, King's College London

Grant type: Project Grant

Duration: 36 months

Amount: £244,581

Scientific Title: Correcting defective endoplasmic reticulum-mitochondria associations as a new therapeutic target for fronto-temporal dementia

Why did we fund this project?

Comments from members of our Research Network:

'A valuable therapeutic target based on sound foundations.'

'The joint prospect of both an improved understanding of mechanisms in FTD and the use of an already approved drug that might be deployed quickly for use in humans makes for an attractive proposal.'

'The use of existing licensed drugs to tackle dementia should be encouraged and supported. The researcher has access to clinical scientists who could quickly move to human trials if the theory was proven in mouse / lab models.'

What do we already know?

Frontotemporal dementia is a form of dementia that causes symptoms including problems with language or changes in behaviour and personality. Currently there are no available treatments for the condition. This may be because the condition affects many different aspects of brain cells and so it is difficult to identify which one is best to target when designing potential treatments.

Two structures inside the cell that are affected are called the endoplasmic reticulum and the mitochondria. The endoplasmic reticulum is responsible for making proteins and fats that the cell needs in order to function; mitochondria act as the energy source for the cell. These two structures help each other to function by exchanging signals, a process that is enabled by a protein attached to the endoplasmic reticulum linking with another protein on the mitochondria, bringing the two structures closer together - a little like two people holding hands. 

Previous research from this group and others has shown that the link between the proteins that tethers the endoplasmic reticulum and mitochondria together is disrupted in frontotemporal dementia. 

What does this project involve?

The researchers have discovered that there is an existing drug, licensed for some liver conditions, that fixes the disrupted tether between the endoplasmic reticulum and the mitochondria. They will further test this drug in brain cells grown in the lab and look at its effect on the tether in great detail using a powerful electron microscope. They will also test the effects of this drug in animals that show symptoms of frontotemporal dementia.

How will this benefit people with dementia?

There are currently no treatments for frontotemporal dementia. Understanding the mechanisms that underlie the condition is a key part in finding ways to prevent or cure it. By focusing on an existing drug, this research also has the potential to bring a much needed treatment to people as soon as possible. Repurposing drugs in this way is a key aspect of our Drug Discovery programme.