From back-room experiments to modern-day clinics
How NHS neurological treatment is underpinned by centuries of research
Imagine, if you will, mid seventeenth-century England: a country seething with political and religious turmoil after the Civil War. Focus your mind’s eye in particular on the university city of Oxford, and the back room of a tavern in a less frequented part of the city. Here we find one Thomas Willis, graduate of Christ Church and member of the ‘Oxford Philosophical Club’ of experimentalists. He is accompanied by Richard Lower, Thomas Millington and Christopher Wren. They have just removed the brain from the skull of a deceased patient, and are preparing to slice it from the base upwards. The year is 1664, and Thomas Willis is 43 years old. He holds the position of Sedleian Professor of Natural Philosophy and believes that the key to understanding the nature of the soul lies in the physiological make-up of the brain. This year, he will write up the results of these dissections in the book for which he will become most well-known: Cerebri Anatome, or ‘Anatomy of the Brain’.
Consider how Thomas Willis may have felt had he known that his efforts would lead to the founding of the discipline of neurology (for in his book he coined this word). What would he make of the modern-day neurologists at Oxford’s John Radcliffe Hospital, seeing patients in clinics for epilepsy, motor neuron disease, Parkinson’s and multiple sclerosis? Many of these clinicians, working in the Oxford University Hospitals NHS Foundation Trust, are also scientists employed by the University of Oxford, continuing Willis’s tradition of experiments and investigation to find out more about the brain. Their aim is perhaps not so much to delve into the philosophical mysteries of the mind, but to work out how to fix the brain when it goes wrong.
In 2018, the year the UK’s National Health Service turns 70, it’s important to celebrate the centuries of research behind today’s NHS treatment for neurological disorders. Our clinician scientists are standing on the shoulders of giants, building on existing knowledge, using what they learn in the laboratory to improve their clinical practice. Let’s cast our eyes over two neurological disorders and some of the latest discoveries made at Oxford that could ultimately benefit patients.
Searching for the origins of motor neurone disease
Amyotrophic lateral sclerosis (ALS) is the commonest form of motor neurone disease (MND) and the third commonest form of neurodegenerative disease after Alzheimer’s and Parkinson’s. MND affects the nerves (motor neurones) in the brain and spinal cord that tell your muscles what to do. Messages from these nerves gradually stop reaching the muscles, leading them to weaken and waste. It is currently incurable, although scientists are confident that it arises for a complex set of reasons, including harmful genetic variants and environmental factors.
Research is held back in part by the lack of an early diagnostic test and predictable indicators of the progression of the disease — these are called biomarkers. Professor Martin Turner, co-director of the Oxford MND Care & Research Centre, explains: ‘Patients still wait too long for a certain diagnosis of MND, and it is possible that future drugs may need to be given at much earlier stages to be most effective. Clinical trials currently require lengthy study times to get a clear answer, and don’t always account for the variability of the disease between patients. We really want to improve this situation’.
Martin can pinpoint the exact moment his interest in the brain was sparked. At the tender age of seven, he suspended a magnet over his head in bed to see whether it would influence his dreams. Not quite the back-room brain dissections practised by Thomas Willis and co., but no doubt carried out in the same spirit of curiosity and inquiry.
In June 2018, Martin and colleagues made a big step towards his aim of ‘trying to put a significant dent in one of the most aggressive neurodegenerative disorders’. They published the results of a study which identifies a new type of potential biomarker for ALS. He worked with biotechnology company Oxford BioDynamics and Harvard Medical School. The team used the Oxford BioDynamics EpiSwitch™ platform to compare the genetic make-up of healthy and ALS patient samples. They discovered a biomarker signature related to the complex changes in the way genes are expressed, called a chromosomal conformation signature (CCS) and part of an emerging field known as epigenetics. This work reveals a highly promising, potential new approach to the diagnosis of this disease.
Spotting the onset of Parkinson’s disease
It’s a similar story with Parkinson’s disease, a disorder of the nervous system causing tremor, stiffness and slowness of movement. The main problem for clinicians is that it’s very hard to diagnose Parkinson’s early enough to offer patients beneficial treatment. By the time they show up in clinic, the disease is already advancing and it is only the symptoms which can be managed, rather than the cause addressed.
The Oxford Parkinson’s Disease Centre, led by Consultant Neurologist Professor Michele Hu alongside Professor Richard Wade-Martins, is making great strides forward on many fronts in the struggle to understand this condition. Most recently, they have been awarded a five-year grant from the NIHR Oxford Biomedical Research Centre to look into the relationship between Parkinson’s and a sleep condition known as Rapid Eye Movement Sleep Behaviour Disorder (or RBD for short). In RBD, the switch that normally turns off movement during sleep is faulty, causing people to move or shout while asleep.
Sleep disorders are interesting for neurologists because they can be an early indicator of problems with the nervous system. Michele and her colleagues are particularly focusing on the link between RBD and Parkinson’s because many people with Parkinson’s are thought to suffer from RBD as well. A person who goes on to develop Parkinson’s may have RBD for many years before the problems begin with their movement when they are awake. So might it be possible to use RBD as a sort of ‘biomarker’ for Parkinson’s?
The first step for the research team is to invite people who are already coming into clinic for an NHS sleep study to wear some new kit at the same time. The recording equipment includes a motion sensor worn on the wrist, a pulse and oxygen sensor worn on a fingertip, and a sleep monitoring device which worn on the head, chest and abdomen. Michele and colleagues in the Oxford Institute of Biomedical Engineering will ‘train’ computer algorithms to correctly interpret the data that the wearable kit collects. The team then hope to recruit people from across the UK who have either RBD or Parkinson’s, to wear the sleep monitoring devices at home for a few nights every six months.
Michele says: ‘My aim is to identify the people with RBD who are at the highest risk of developing Parkinson’s before their symptoms appear. If we can do this, it may allow us to start them on treatment to slow down or even prevent the onset of Parkinson’s.’
70 years of the NHS — 350 years of neurology
Next time you visit the John Radcliffe or indeed any hospital, take a moment to consider the hundreds of years of medical discovery underpinning the treatment that the doctors offer you or your family and friends. Without those first somewhat grisly experiments in dingy back rooms, and without the continuing painstaking laboratory research in our university hospitals, the NHS would simply not exist. So let’s celebrate those 70 years, but let’s also celebrate the science behind the treatment.
Find out more about the Nuffield Department of Clinical Neurosciences and follow them at @NDCNOxford.
Written by Jacqueline Pumphrey, Communications and Public Engagement Officer, Nuffield Department of Clinical Neurosciences.
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