Identifying molecular changes in FTD
Prof Adrian Isaacs
University College London
24 September 2018 - 24 September 2021
Full project name:
Identification and characterization of novel modulators of C9orf72 FTD RAN translation
Prof Adrian Isaac's research student, Benedikt Holbling from University College London will look to identify molecular changes during Frontotemporal dementia (FTD).
Frontotemporal dementia (FTD) is the second most common cause of dementia in the under 65s.
It causes devastating symptoms of personality and behaviour changes, lack of empathy, and communication problems, and there are currently no specific treatments available for those affected.
To add further tragedy to those affected by FTD, around 10% of cases are genetic, meaning the disease is passed down in families.
Over the past years, researchers have been working hard to pinpoint the faulty genes that cause genetic forms of FTD and learn more about how they cause the disease.
This will help researchers to identify the toxic mechanisms that damage nerve cells in the brain and to look at ways to develop new medicines that block these processes and treat the disease.
What will they do?
Research student, Benedikt will use a series of experiments to look at the effect of different approaches designed to target translation and limit the production of toxic proteins.
He will do this in collaboration with the Alzheimer’s Research UK UCL Drug Discovery Institute.
By looking at large numbers of potential genetic modifiers, the team will be able to identify the genes that they could target to help reduce the number of toxic dipeptide repeats.
Nobel-prize-winning stem cell techniques allow the team to study nerve cells in the laboratory that have been grown from skin cells donated by people with FTD caused by the faulty C9orf72 gene.
This allows them to quickly check the effect of a huge number of modifiers in nerve cells that have many of the same features as the people they are trying to help.
Finally, they will use fruit flies that are genetically modified to express the faulty C9orf72 gene.
This will allow them to study in detail the effect of potential translation modifiers on nerve cells and crucially if they can rescue the reduced lifespan caused by the dipeptide repeats.
Frontotemporal dementia or FTD (sometimes called Pick’s disease) is a relatively rare form of dementia.