Can we target the brain’s immune system as a potential therapy for frontotemporal dementia?

Lead Investigator: Dr Sarah Ryan

Institution: University of Manchester

Grant type: Alzheimer’s Society Dementia Research Leader Fellowship  

Start date: October 2023

Duration: 5 years  

Amount: £512,513.13 

Project summary

Dr Sarah Ryan’s research aims to understand the role of brain’s immune cells, microglia, in frontotemporal dementia, and whether addressing brain inflammation could be a new therapeutic target.

Project background

Frontotemporal dementia (FTD) is the second most common type of dementia affecting younger people. People with FTD experience many debilitating symptoms, and sadly there are no treatments available today.  

One of the features of FTD is brain inflammation. In FTD, a type of the cell from the brain’s immune system, called microglia, contribute to brain inflammation when they become aggressively overactive. We know that microglia are overactive in the brains of people with FTD, but we don’t know what causes this.

An error in a gene called C9orf72 is the most common cause of FTD, accounting for 1 in 12 cases. The faulty C9orf72 gene can produce other, abnormal proteins, which are not usually present in the healthy brain. These abnormal proteins can kill brain cells and could be the cause of brain damage that leads to the symptoms of FTD.  

If we knew exactly how the abnormal proteins damaged the brain, this would help us to design new medicines to treat FTD.

Previous work by Dr Ryan showed that the abnormal proteins made from the faulty C9orf72 gene activated microglia leading to inflammation through a specific pathway called the inflammasome.

Dr Ryan aims to find out more about how microglia are activated in FTD and how this leads to symptoms of dementia. 

What does this project involve?

Dr Ryan and her team will use a mouse model of FTD which mimics the brain environment of people with C9orf72-related FTD. By using genetic tools and drug treatments, Dr Ryan will try to prevent the microglia from becoming overactive and reduce inflammation.

Ultimately Dr Ryan hopes this approach will improve the symptoms of FTD.

Dr Ryan will also be able to investigate the complex mechanisms which activate microglia in the brain.

FTD is an understudied topic, and through her research, Dr Ryan will be able to provide the research community with essential new information about the role of microglia in disease.   

How will this project help people with dementia?

By investigating how microglia change in FTD, we can find out more about the disease processes. This will help researchers to design new treatments for FTD in the future.

Dr Ryan is investigating several drugs which are already available for other conditions. If this research is successful, we may be able to re-purpose these drugs to treat FTD.