Using stem cells to target tau
Dr Selina Wray
University College London
1 April 2017 - 31 March 2021
Full project name:
Investigating the role of tau in dementia using patient-derived cell models: distinct mechanisms or common endpoint?
Researchers from UCL are revealing crucial insights into why the protein ‘tau’ behaves unusually in diseases like Alzheimer’s and FTD.
For most of us, a protein called tau is an important protein that helps to maintain the structure and health of our cells.
Dr Selina Wray is exploring why tau behaves unusually in these conditions, investigating how changes in the protein cause damage to nerve cells in the brain.
In diseases like Alzheimer’s, the worsening of symptoms over time is partly due to the spread of damage – Dr Wray is looking at this, focusing on how the damaging processes are transmitted between cells.
The tau protein can also form tangles in different ways, so while the protein is involved in both Alzheimer’s and FTD, the type of tau building up can differ between diseases.
This is another key focus for Dr Wray, who is looking for any differences in the tau protein between different forms of dementia.
This knowledge could allow future treatment approaches to be more targeted, so more likely to be successful.
Why is this important?
Together, Alzheimer’s disease and FTD account for over 70% of all cases of dementia. Existing treatments for people with these conditions can help symptoms temporarily, but they don’t affect the underlying disease processes.
By picking apart the detail of how tau behaves in Alzheimer’s and FTD, this Fellowship has the potential to reveal a number of crucial insights.
Any new biological mechanisms that Dr Wray is able to identify – in the development of tau tangles, the way they affect nerve cells, or the way tau might contribute to the spread of damage around the brain – is a potential target for a new dementia drug.
The findings from this Fellowship can feed directly into early drug discovery programmes that take these biological processes to search for experimental drugs that can block them.
Anything that could alter tau’s toxic effects would have the potential to offer renewed hope to hundreds of thousands of people with dementia across the country.
What will they do?
Dr Wray is using a Nobel Prize-winning technique in this project, taking skin cells donated by people with a genetic form of Alzheimer’s or FTD and turning them into stem cells – cells that have the potential to become any type of cell in the body.
Dr Wray is transforming these cells into nerve cells similar to those found in the brain.
Dr Wray and her team are carefully monitoring how tau develops in these nerve cells, looking to identify the exact points in each disease at which the protein begins to behave unusually.
Investigating the similarities and differences of tau build-up in these diseases will help to uncover whether both diseases can share any future treatments and diagnostic strategies, or whether they may each require a more tailored approach.
Dr Wray and her team are also studying the way that nerve cell processes change in people with Alzheimer’s and FTD.
They are looking at whether they can change the way nerve cells are affected by altering the behaviour, or amount of tau present.
The team is also introducing abnormal tau into healthy nerve cells, to see if this kick-starts a cascade of damage, helping to explain how these diseases spread across the brain.
David Hague Early Career Investigator of the Year 2018
Dr Selina Wray was the winner of the David Hague Early Career Investigator of the Year Award 2018 for her outstanding contribution to the tau biology field.