‘Defending the brain’: one year on

brain

This time last year, Josie Dixon wrote an article in Oxford Today about dementia, for which she interviewed OxDARE’s coordinator, Clare Mackay.  The Prime Minister’s Challenge on Dementia (which initially prompted the formation of OxDARE) led to a huge influx of government funding in 2014, providing the means to improve existing biomedical research infrastructure and resulting in the growth of new areas of research activity.

Returning to interview Clare Mackay, the biggest development over the past year has been the change in the way scientists in this field now work: following successful funding applications in 2014, there has been a move towards large-scale collaborative research. These research platforms include the Dementias Platform UK, Alzheimer Research UK’s Drug Discovery Alliance, and the European Prevention of Alzheimer’s Dementia (EPAD). All three have Oxford academics in the leadership (John Gallacher, Richard Wade-Martins and Simon Lovestone) and involve a vast number of people. In terms of the culture shift, Mackay states that ‘we are still finding our feet; the dust hasn’t settled yet as far as figuring out how this new way of working is going to develop’. She likens this large-scale group work to developments in particle physics, where people from around the world came together to create – and subsequently share – the Large Hadron Collider. Because dementia is also too big and too complex a problem for any individual or small group to ‘solve’ on their own, it is increasingly apparent that we need to replicate the sort of well-funded, highly collaborative environment that led to the discovery of the Higgs Boson.

Mackay believes that pooling efforts is a sensible thing to do from a political point of view, but it is also necessary to find a balance between harnessing the collective power of a group and giving people the space and time to be individually creative. Another challenge is the inevitable fact that some people feel excluded. Although new scientists are very much welcomed, there are a number of anxieties both for those who are involved and those who remain outside of these collaborations. Mackay notes that all academics have to bring in money to their universities, but in large platforms there are fewer opportunities to be the named Principal Investigator on a grant. Therefore it will be necessary to find ways to give appropriate reward to individual scientists, particularly those who are in the relatively early stages of their careers.

One example of a platform activity that would be impossible to do without a collaborative group of scientists is the Deep and Frequent Phenotyping study. ‘The aspirations of this study are to find ‘biomarkers’ that are sensitive to the earliest changes in Alzheimer’s disease’, says Mackay. For decades people have been trying to find biological markers that signal the changes that occur in the brain prior to the onset of Alzheimer’s disease, but each group of scientists has been looking in their own sphere of interest. In the words of Simon Lovestone: ‘inevitably the cognitive scientists are looking for a cognitive test, the imaging scientists for an imaging test, and bioscientists for a blood test and then there are the newer ideas, such as assessing gait’. But it is difficult to compare and contrast these types of markers because they are never studied in the same patients over the same period of time.

The best way of characterising the early changes in Alzheimer’s disease is almost certainly going to be through a combination of biomarkers, so the idea behind this intensive study is to carry out the first head-to-head comparison of these different types of markers. A feasibility study is underway to test the tolerability for patients and the logistics of doing this type of study across 6 sites in England.

At this point in time, biomarkers are needed to place people in clinical trials and to assess whether the trials are working. As such, the discovery of biomarkers are one of three advances in biomedical science that Mackay sees on the horizon. The others are the focus on drug development and the growing importance of ‘big data’ and informatics in dementia research. This biomedical research is happening alongside the other strands of the Prime Minister’s Challenge on Dementia, namely creating dementia-friendly communities and improving medical and social care for people with dementia.

Whilst the aim of this research is to reduce the number of people who have dementia in the future, it does not address the needs of those who are currently living with this disease. Back in Oxford, new developments at the Oxford Centre for Human Brain Activity (OHBA) may help to change this: a new assessment service for cognitive health will be developed that includes state of the art imaging and cognitive testing alongside clinical assessments. The aim is to bridge the gap between academic research and the clinic (known as the ‘translational pathway’) by reducing the amount of time it takes for research developments to become part of routine clinical practice. The building work is scheduled to be completed by Spring 2016, with the assessment service developed in the year after that: ‘our challenge is not only to enable high-quality assessments for people who are concerned about their cognitive health, but also to make the information that we are collecting accessible and useful to memory clinicians, GPs and the patients themselves.’

Returning to the role of OxDARE in this changing landscape, Mackay states: ‘my ambition for OxDARE is that it creates a structure in which a community of scientists from different disciplines feel that they can work together. I want it to be a melting pot of ideas and an enabler for people to be creative.’ With members of OxDARE contributing to all of the projects mentioned above, the next 12 months look just as promising as the last.

 

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