By Professor Nick Fox, Co-Chair of the Leonard Wolfson Experimental Neurology Centre, Director of the UCL Dementia Research Centre
Dementia directly affects over 850,000 people in the UK, a number that is set to rise in the coming years. Dementia has an impact much wider than the individual who is affected – it is devastating for all those who care for, and care about, that person. Polls show that dementia is now the most feared medical ‘condition’ in the UK. The most common causes of dementia are neurodegenerative: diseases such as Alzheimer’s disease and Huntington’s disease where brain cells degenerate, resulting in progressive cognitive and functional decline. Dementia has been described as the ‘challenge of our age’ and it is a global priority to find therapies that can slow, delay or prevent its onset.
Early intervention
In 2011, UCL was awarded £20 million under the Wolfson Neurology Initiative, an international competition to support outstanding research with the potential to improve the understanding and treatment of neurodegenerative conditions.
At that time, there had been huge advances in conditions like cancer and HIV, but progress was lacking in neurodegenerative diseases, despite increasing recognition of the scale of the problem.
It was becoming clear that earlier interventions might be a more effective way to tackle these diseases. There was increasing evidence that there was a long ‘silent’ period when changes happened in the brain, but people did not have symptoms. This was a window of opportunity we needed to understand better. At the same time, we needed a safe environment to trial biologically active and invasive treatments, as well as the staff and the expertise. This was the basis for our application to Wolfson.
The Leonard Wolfson Experimental Neurology Centre
The Leonard Wolfson Experimental Neurology Centre opened at UCL in 2013, a legacy to the late Chairman of the Wolfson Foundation. It created a new Clinical Research Facility and associated research programmes aimed at understanding and treating neurodegenerative diseases as early as possible, ideally even before symptoms. It also created a training programme for clinicians and scientists to develop the next generation of research leaders who will be critical to advance the search for therapies.
The Leonard Wolfson Experimental Neurology Centre at the UCL Queen Square Institute of Neurology
The Clinical Research Facility was the first of its kind – a facility dedicated to neurodegeneration. Trials can now take place in a safe environment at the National Hospital for Neurology and Neurosurgery in London. Having a dedicated space with a trusted team of researchers and clinicians with patients’ best interests at heart has driven patients’ confidence in and enthusiasm for taking part in trials.
Landmark research
Thanks to this facility, the Centre has enabled some truly landmark studies. These include breakthroughs in treatments for Alzheimer’s disease and Huntington’s disease, as well as critical advances in other diseases, from Parkinson’s to frontotemporal dementia. These advances have been alongside remarkable improvements in diagnostic methods that will be so important for clinical practice and for trials.
Breakthrough in Huntington’s disease
The progress made in Huntington’s is a good example. Huntington’s is a devastating genetic disorder that causes progressive cognitive, behavioural and movement problems that can start early in adult life. Sadly, it can lead to death within a few years, or may last decades.
My colleague at UCL, Professor Sarah Tabrizi, was able to conduct the first study in humans that showed that a gene therapy could not only reach the brain, but also reduced the levels of the harmful protein made by the gene. This was an ambitious and challenging study, not least because the treatment had to be given via an infusion into the cerebrospinal fluid – fluid that surrounds the spinal cord. This meant patients taking part in the trial had regular invasive lumbar punctures. Remarkably, the study had almost no drop-outs, which is virtually unheard of. This was because of the dedication of the participants, but also because they felt safe and valued, with staff who knew them by name.
Trial therapies for Alzheimer’s
We also completed a trial of a disease-modifying therapy for Alzheimer’s, which became the first treatment licensed by the US Food and Drug Administration (FDA) on the basis that it removed a key disease-causing protein called amyloid from the brain.
We’ve known for over 100 years that amyloid build-up in the brain is a key feature of Alzheimer’s disease. Our study at the Leonard Wolfson Centre showed that we can use drugs to remove these amyloids. Whether this will turn into a cure for Alzheimer’s, we don’t know, but it is providing hope that we can change the biology in the brain.
In parallel, we are conducting studies in inherited (or familial) Alzheimer’s disease. We are aiming to show that we can slow or delay the onset of disease in those who carry a gene that causes early onset dementia. Having worked with these families for many years, I am now seeing the children of those who first took part in my research starting to become affected themselves. This is an aim that is particularly close to my heart, and one where we need to make urgent progress.
Wide-ranging impact
The Leonard Wolfson Centre has had more of an impact than I ever would have hoped – in several ways. The next generation of neuroscience researchers have been supported through an education and training programme for PhD students and are now leading labs around the world.
We’ve also set up the first biomarker lab for dementia. Biomarkers act like an early warning system. By monitoring cerebrospinal fluid, blood, urine, or other tissues, we can detect changes at the cell level. The lab at the Leonard Wolfson Centre serves 100 hospitals across the UK, meaning that this expertise can be shared.
And the Centre has been a catalyst for other projects, including the UK’s Dementia Research Institute, headquartered at UCL with six centres across the country. We’re now building a UCL neuroscience facility at 256 Grays Inn Road that will bring together patients and researchers, building on the model of the Leonard Wolfson Centre.
Sophie’s story
Most of all, I am committed to and humbled by the families who take part in our studies. I have got to know Sophie, who knew she had a 50 per cent chance of carrying a rare genetic mutation which would see her develop dementia early in life. In 2015, she joined a study at the Leonard Wolfson Centre in the hope that she could help researchers understand how Alzheimer’s develops – and perhaps help future generations.
Sophie recently discovered, by deciding to have a genetic test, that she will develop early-onset Alzheimer’s. Facing this diagnosis, she says:
Taking part in research has given me something positive to focus on… I strongly believe that something will be learned from it that will help guide future research.
This is hopefully only the beginning of a new era of effective therapies and of hope.
In 2011 UCL was awarded £20 million under the Wolfson Neurology Initiative, an international competition to support outstanding research to improve the understanding and treatment of neurodegenerative conditions. Find out more about the work of the Leonard Wolfson Experimental Neurology Centre.
