Research

Spotlight on: Neurodegenerative diseases: dementia

What are neurodegenerative diseases?

Neurodegenerative diseases are incurable conditions in which nerve cells gradually degenerate, or die, for reasons that are not yet understood. There are many neurodegenerative diseases – such as Alzheimer’s disease, Parkinson's disease, Huntington's disease, motor neurone disease, Creutzfeldt-Jakob (prion) disease and multiple sclerosis. Many of these give rise to dementia, which represents a major and growing public health burden.

The dementias are a group of neurodegenerative diseases characterised by varying degrees of memory loss, mood changes and communication problems, depending on the disease and stage of illness. Although dementia is associated with Parkinson’s disease, motor neurone disease and Down’s syndrome, Alzheimer’s disease accounts for more than two-thirds of all dementia cases. There is currently no cure for Alzheimer’s disease, but researchers are working hard to find new treatments that can delay and potentially prevent the disease.

A global challenge

The dementias are one of the toughest medical and economic challenges facing our society today. Around 850,000 people in the UK suffer from dementia, costing the health care system over £26 billion a year. And the incidence of dementia will continue to grow as the population in the UK and Europe ages, with the number of people affected predicted to double within the next 20 years.

Faced with these statistics, the 2013 international G8 Summit on dementia in London, led by David Cameron, called for action to tackle this global challenge. Crucially, this will involve developing new dementia therapies. Very few treatments are currently available for people with dementia, and those that do exist just treat the symptoms or are effective at only some stages of disease. There are no available treatments that can stop or reverse the degeneration of brain tissue. This is primarily because our understanding of how dementia develops is very limited. The brain is a highly complex organ and it is difficult to unpick the different biological processes that are involved in the degeneration of nerve cells. As a result, drug development so far has been largely ineffective.

New research

Professor Julie Williams (click to read more)
Professor Julie Williams is an MRC scientist who has discovered five genes that predict a person’s risk of developing Alzheimer’s disease.

Fortunately, new research opportunities are emerging. These combine different scientific approaches such as genetics, brain imaging, stem cell models of disease and large-scale population-based studies. Bringing together data from these scientific areas will speed up scientists’ ability to figure out how neurodegenerative diseases develop, which will in turn improve our understanding of dementia and help us to find new treatments for patients.

A key focus of current dementia research is on disease mechanisms. Learning more about these mechanisms will help us to develop more effective treatments and, potentially, find ways of preventing dementia from developing in the first place. A useful way of studying disease mechanisms is to create stem cell models. These are stem cells that have been ‘shaped’ into the nerve cells of a particular disease, so that they represent the brain tissue of patients who have, or are at risk of developing, that disease. Dr Rick Livesey is an MRC-funded scientist in Cambridge who is using this technique to work out the cellular and molecular basis of Alzheimer’s disease. By growing stem cell models of different forms of Alzheimer’s disease and uncovering the differences between them, Rick hopes to shed light on how the disease develops.

Another MRC researcher, Professor Julie Williams, from the MRC Centre for Neuropsychiatric Genetics and Genomics Neuropsychiatry in Cardiff, is exploring the genetic basis of Alzheimer’s disease. Her team has designed powerful studies with thousands of patients, allowing them to discover five genes which strongly predict a person’s risk of developing the disease. “If we can remove the bad effects of these genes through treatments,” says Julie, “we may help reduce the number of people developing Alzheimer’s in the future.”

Professor Anthony Schapira at University College London is similarly looking at the genetic roots of dementia, but with a focus on Parkinson’s disease. An important risk factor for Parkinson’s disease is a mutation in the GBA gene which causes it to stop working. People with specific GBA mutations are 20-30 times more likely to develop Parkinson’s disease. Anthony is studying a group of more than 200 people with GBA mutations to find out what the molecular mechanisms are behind this increased risk. Through new MRC funding, he is also testing whether a new drug could counteract the loss of GBA gene function in these patients. If successful, this could lead to a potential therapy for patients.

Alongside research into disease mechanisms, scientists are designing tools that can help doctors diagnose dementia earlier and more accurately. One such tool is CANTAB, which picks up the early signs of dementia by testing different areas of cognitive function, such as memory, attention, reaction time and decision-making. Part funded by the MRC, CANTAB is now available to use on iPads and a number of GP practices in England have already signed up to use this technology as part of their service. Delbox is another diagnostic tool which has been developed by MRC-researcher Professor Alasdair MacLullich, from the Centre for Cognitive Ageing and Epidemiology at Edinburgh. It has been designed to diagnose delirium among older hospital patients, which is a major risk factor for dementia.

Importantly, scientists are also improving the testing of new drugs through better clinical trials. Testing drugs at all stages of their development is vital for making progress in dementia research. MRC researcher, Professor Seth Love at the University of Bristol, is researching whether zibotentan, a drug which failed to treat prostate cancer, could be used to fight the symptoms of Alzheimer’s disease by increasing the brain’s blood supply. Seth will first test the drug in rats before then moving on to human trials. In another MRC-funded study, Professor Robert Howard, from King’s College London, is assessing the effects of donepezil, the most commonly prescribed drug for the early stages of Alzheimer’s disease. Robert has shown for the first time that donepezil can help patients who are in the moderate to severe stages of Alzheimer’s disease by slowing down the progression of the disease. This is an exciting finding which suggests that the drug could help many more patients than previously thought.

Ultimately, the success of dementia research will depend on scientists working together with industry. This will provide the opportunities for scientific findings to be translated from the lab into the clinic where they can help patients.

How is the MRC involved?

The UK Dementia Research Institute (DRI)

A joint investment of £250m from the MRC, Alzheimer’s Society and Alzheimer’s Research UK will create a national Institute which will bring together world-leading expertise in biomedical, care, public health and translational dementia research. Centred around the need for innovative, discovery science to unlock our understanding of the mechanisms underlying the development and progression of dementias, the DRI’s research will invigorate the therapeutic pipeline and drive new approaches to diagnosis, treatment, care provision and prevention.

The new Institute will be catalytic for the UK's dementia research effort, and will be built in a way that optimally connects existing capabilities within the UK research landscape and engages emerging research opportunities. The DRI will also proactively seek industry and international partners in delivering its mission.

In December 2016, the DRI Director and Hub location were announced, marking a huge step forward in the Institute’s establishment. Throughout 2017, Centres across the UK will be selected to become part of the DRI and recruitment will take place to attract leading researchers across different disciplines. 

Providing resources

In order to study neurodegenerative diseases, such as dementia, scientists need access to high-quality samples of brain tissue. In 2009 we established the UK Brain Banks Network, which links together ten brain banks to provide high-quality brain tissue that researchers can use to study neurological and psychiatric diseases, including the dementias. Prior to this, researchers had to apply to each brain bank separately to find the samples they needed. Now they can access samples from over 9,000 donated human brains through the Network’s online database, providing one of the world’s largest resources of its kind. In future, the Network will be linked to major cohort studies through the MRC Dementias Platform UK (DPUK; see below) so that the samples can be matched with patients’ health records during their lifetimes.

Working together to tackle obstacles

Our partnerships with universities, charities and industry are an important part of our activity in neurodegeneration research. We have partnered with the Wellcome Trust to invest £17 million into three major collaborative research programmes, which have provided important insights into the disease mechanisms underlying Alzheimer’s, Parkinson’s and motor neurone disease. We have also established two brain ageing research centres in Edinburgh and Newcastle, and increased our investments in neurodegeneration research at the MRC Laboratory of Molecular Biology, the MRC Cognition and Brain Sciences Unit in Cambridge, and in brain-related genetics research at the MRC Centre for Neuropsychiatric Genetics & Genomics Neuropsychiatry in Cardiff.

National programmes

Dementias Platform UK (click to read more on our Insight blog)
 
The DPUK is taking a more holistic approach to dementia research. Click on the image to watch an interview with Dr John Gallacher, Director of DPUK, in which he explains what the DPUK is all about.

In 2014 we launched the new MRC Dementias Research Platform UK (DPUK) as a world-leading programme to speed up progress in dementias research. DPUK will connect academic research centres with UK and international biopharmaceutical companies to create a single resource that brings together data from over twenty population and disease cohort studies. Together these studies involve nearly two million participants. Analysing whole-body data on such large numbers of people will give us enormous statistical power to study what happens to our bodies as we age and enter the early stages of neurodegenerative disease. Ultimately, the Platform will help us to translate this scientific knowledge into new interventions and therapies that could one day prevent or delay dementia and lead to a better quality of life in older age.

We will provide £12 million to support the DPUK over the next five years, with industry providing another £4 million. We are also planning to invest a further £45 million in 2015-2016 to provide new equipment and informatics resources for DPUK and associated research groups across the UK.

Read more about the Platform and what it hopes to achieve in a post on the MRC blog, Insight. 

A central component of DPUK is UK Biobank. This is a major national health resource co-funded by the MRC and the Wellcome Trust which is collecting information and biological samples on the health and lifestyles of half a million volunteers in the UK. This wealth of data will be used to look at the effects of our genes, lifestyles and the environment on our health and on different diseases. To help scientists discover some of the brain changes that are linked to dementia, we have provided funding to scan the brains of up to 100,000 Biobank participants. In the future, UK Biobank will map the genetic make-up of all 500,000 volunteers to discover how our genes contribute to neurodegenerative disease.

Going global 

Our activity in dementia research extends beyond the UK, with the MRC leading the development of two international collaborations. The Joint Programming in Neurodegenerative Disease (JPND) and the Centres of Excellence Network (COEN) initiatives are pooling together the resources of the UK and up to 28 other countries to find causes of neurodegenerative diseases, develop cures, and identify the best ways to care for people who are suffering with these diseases. Among other activities, JPND is working on maximising the use of valuable cohort studies across member countries. And COEN is funding ‘pathfinder’ scientists who have come up with new approaches to understand neurodegenerative disease mechanisms and develop new drugs.