Stuart Pickering-Brown, Professor of Neurogenetics at The University of Manchester, has been awarded £1million from the Medical Research Council to study a common cause of dementia.
Frontotemporal Lobar Degeneration (FTLD) is the second most common cause of dementia after Alzheimer’s disease and is related to motor neurone disease. Around 40% of patients with FTLD have a family history of dementia, indicating that genetics plays a large role in the development of the condition.
Professor Pickering-Brown, from the Institute of Brain, Behaviour and Mental Health, said: “We know of several genes that cause FTLD, one of which is called C9orf72. However, we don’t fully understand how mutations in this gene lead to dementia.”
The new research aims to look at the repeat expansion mutation of C9orf72, the most common genetic cause of FTLD and motor neurone disease. This repeat expansion mutation of C9orf72 produces five different repetitive proteins that accumulate in brain cells.
The team intends to create models of four of these five repetitive proteins to hopefully mimic aspects of FTLD. They will then investigate if these repetitive proteins contribute to the processes that cause brain cells to die.
Professor Pickering-Brown and his team are the first to make the expansion mutations of a physiologically relevant size, matching those which are observed in patients. Other researchers around the world have previously used a much smaller mutation repeat sizes not seen in patients.
In addition, with the help of the Manchester Brain Bank and the UK Brain Bank Network, the research team will measure levels of these five proteins in the brains of people with the C9orf72 gene mutation, to see if levels of proteins affect the disease presentation or pathology.
Ultimately, is it hoped their work will offer a platform for researchers to test therapies for FTLD.
Grant application entitled ‘C9orf72 Dipeptide Repeat Proteins: molecules and Models’.