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One examines cells, the other examines patients.
Together they are working to fight dementia.

Words Anne Wollenberg Photograph Alun Callender


If you’re in your 50s and your spouse starts acting strangely, you wonder if there’s a problem in your marriage

If you carried a faulty gene that caused dementia, would you want to know? This is the tough question faced by patients who participate in research at the UCL Institute of Neurology and Dementia Research Centre at Queen Square, where Dr Selina Wray and Dr Jonathan Rohrer are part of a large and prolific team working on frontotemporal dementia, or FTD, one of the most common causes of dementia in under 65s.

But what makes someone develop dementia symptoms? Why can we carry problem genes for years before showing outward signs of disease? And can we slow this down or even stop it altogether?

“Younger-onset dementias are hugely under-recognised,” says Rohrer, MRC Clinician Scientist and Honorary Consultant Neurologist at the National Hospital for Neurology and Neurosurgery. “For these patients, symptoms often appear during their 40s, 50s or 60s. Many are still working and they may have young children.”

Rohrer is following a group of people in their 20s and 30s whose parents developed FTD. Each has a 50 per cent chance of inheriting mutations in genes such as tau, which leads to the disease. They undergo a range of tests including MRI scans, blood and spinal fluid tests, and psychological tests to check for problems with language and social cognition.

Tau is an important protein in the brain. In cases of dementia, however, it forms harmful build-ups and cells eventually react by dying off. Dr Wray, Senior Research Associate, Molecular Neuroscience, is examining this process in the lab, seeing how pluripotent (genetically reprogrammed) stem cells react to build-ups of tau protein.

“Our work relies on collaborating with clinicians to access cells from patients,” she explains. “A lot of traditional modelling was done with animal cells or human cells that are not neuronal, because it wasn’t possible for us to access and grow human brain cells in the laboratory.

“In the last seven years, we’ve used a new technique that lets us take a piece of skin from a patient’s arm and use this to create brain cells. This has completely revolutionised the way we model diseases.”

As a result, she says, “the cells I use in the lab come from the same patients who give blood and have MRI scans. We can grow cells in a dish, see the differences between patients who do or do not have dementia and use them to understand what is going wrong in diseased cells.”

Some participants wish to know if they carry the mutation, but most do not. Wray believes this would change if treatment was available. “If you knew you could take a drug to slow down the disease, it would change the implications of knowing you carry the gene,” she points out.

“FTD really gets to the core of who you are and changes how you act around other people,” explains Rohrer. “This can include loss of empathy, saying ruder things, being more obsessive and hoarding. It can be hard for people to recognise that these symptoms are part of a brain problem. For example, some of the people we see have been through relationship counselling. If you’re in your 50s and your spouse starts acting strangely, you wonder if there’s a problem in your marriage.”

It is harder for people to recognise that a brain problem may be the cause. Wray points out that diagnosing FTD can also be challenging for GPs, “who are not specialists in all sub-types of dementia”.

These are genetic conditions that you are born with, says Rohrer, “meaning we don’t know a lot about what the triggers are and why, if you have this genetic problem all your life, it takes until your 40s, 50s or 60s to develop. It isn’t the case that nothing is happening in the years before people develop FTD. The disease is already happening, but your brain is able to compensate up to a point”. This indicates a window of opportunity, says Wray, “in which we can intervene to either stop the disease altogether or simply slow it down. Either would be an incredible leap forward”.

A recent paper detailed some of the early changes that can be seen with tau protein. “Our next step is to use those cells to develop a drug trial.”

Work that Rohrer has recently performed shows that psychological changes tend to appear around five years before the onset of FTD symptoms. Changes in brain imaging can be seen 10-15 years before.

“If we want to be successful in developing treatments, we need ones that will intervene in these very early stages,” says Wray. “It is essential that the basic science and clinical research go very much hand in hand.”

“A key goal is for us to move closer together,” agrees Rohrer. “We are now at the stage where we can develop and screen drugs with the aim of testing them in patients – moving them from one part of Queen Square to another. In previous years, I’ve told people that they will be helping future generations. Now I am able to tell participants that I think they will be in the very first drug trial.”

Dr Rohrer and Dr Wray, pictured above at the National Hospital for Neurology and Neurosurgery, have set up www.ftdtalk.org to provide clear, accessible information about frontotemporal dementia.

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Portico Issue 2. 2015/16