Understanding the role of the C9orf72 gene in frontotemporal dementia

Research project: Dissecting the contribution of dipeptide repeats to toxicity in C9orf72 iPS-derived neurons from ALS/FTD patients

Lead Investigator: Dr Kevin Talbot 
Institution: University of Oxford
Grant type: PhD studentship
Duration: 36 months
Amount: £84,950

Why did we fund this project?

Comments from members of our Research Network:

“The study has the potential to make progress and solve another part of the puzzle.”

“Good to see one of the rarer dementias being researched.”

“Good expertise and facilities to undertake this research.”

What do we already know?

Frontotemporal dementia is a rarer form of dementia that usually affects people under the age of 65. Some frontotemporal dementia cases have a known genetic link, but in the majority of cases the cause is unknown. 

One of the genetic forms of frontotemporal dementia has been closely linked to motor neuron disease (also known as amyotrophic lateral sclerosis or ALS). Both of these conditions affect the nerve cells and can affect members of the same family, and some people may experience both conditions. 

Changes to a gene called C9orf72 have been linked to the development of both frontotemporal dementia and motor neuron disease. When this gene is damaged, it produces faulty proteins that form clusters. These clusters appear to cause damage to nerve cells in both conditions.

What does this project involve?

The researchers will take skin cells from people with the genetic changes in C9orf72 that are associated with frontotemporal dementia or motor neuron disease. These skin cells will then be ‘reprogrammed’ to their earliest form, known as a stem cell. These stem cells will then be transformed into nerve cells. These programmed cells, called induced Pluripotent Stem Cells (iPSCs), allow researchers to examine brain cells from people with dementia. 

The researchers will compare the brain cells that they generate from people with C9orf72-releated frontotemporal dementia to those of people who don’t have the condition. 

The researchers will use these cells to understand how the protein clusters caused by the changes to the C9orf72 gene affect the cells. They will turn the gene’s activity on or off to see if there are any stages where the nerve cells can get rid of the clusters.

How will this benefit people with dementia?

There are currently no treatments for either frontotemporal dementia or motor neuron disease. The C9orf72 gene is thought to be a key contributor to both conditions, and better understanding its role will help researchers to uncover more information about the underlying processes behind the diseases. Understanding how C9orf72 affects cells will also help researchers to uncover potential targets for future treatments.  

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