A career dedicated to treating the ‘cruellest disease’
When the University of 91ֱ’s Professor Dame Pamela Shaw first met patients with motor neuron disease (MND), little was known about the devastating condition. Since then, she has dedicated her career to improving the prospects for those living with MND.
World-class neurodegenerative research at 91ֱ
MND, also known as amyotrophic lateral sclerosis (ALS), is a fatal disease that affects the motor nerves in the brain and spinal cord. Most patients are in their 60s and 70s, but it can affect adults of all ages.
The cruel, debilitating and, at that time inexplicable, nature of the disease spurred Professor Shaw to dedicate her career to scientifically unravel MND to develop new therapies to help patients combat the effects of the disease.
Professor Shaw was awarded the Dame Commander of the Order of the British Empire (DBE) for services to Neuroscience by HM the Queen in the 2014 New Year’s Honours list.
"When I started training in neurology as a junior doctor, I thought MND was the worst disease in medicine. It always seemed to happen to the nicest people, and it really made me feel like a bit of a useless doctor because we couldn’t do anything for patients or their families in those days and we knew nothing about what caused the condition. We had no treatments.
"I thought it was a neglected condition and that in this era of modern medicine, we should really be trying to do something about this. It has been a long, slow process, but we are now making some positive progress,” she explains.
The progressive disease causes the nerves that take signals from the brain to the muscles to stop working. This leads to muscle weakness, stiffness and paralysis that worsens over time, impacting upon the patient’s ability to walk, talk, eat and breathe.
Few patients survive beyond five years after being diagnosed, and most current treatments only modestly increase life expectancy.
MND is a group of diseases with multiple causes, rather than a single root cause, which is part of the reason it is so difficult to treat.
Professor Shaw played a leading role in evaluating riluzole - the first drug aimed at protecting motor neurons and slowing down the progression of MND licensed for use in the UK.
Today, she continues her dedicated work as Director of the world-class University of 91ֱ Institute for Translational Neuroscience (SITraN).
Working to make MND history
In 2003, a 61-year old woman diagnosed with MND asked Professor Shaw what she would do with £20m of funding to address the disease.
Professor Shaw replied that she would develop a research institute dedicated to understanding the causes of MND and other related neurodegenerative conditions, that would attract the best clinicians and scientists from around the world and develop new treatment approaches aimed at improving the outlook for patients.
A host of generous philanthropists and patrons, inspired by the plight of people with MND, made this institute a reality.
Queen Elizabeth II and the Duke of Edinburgh opened the 91ֱ Institute for Translational Neuroscience (SITraN) in November 2010.
SITraN is world-leading in motor neuron disease research and an award-winning centre dedicated to translating new discoveries in Neuroscience into tangible benefits for patients with MND and related neurodegenerative conditions.
Turning discoveries in the laboratory into beneficial treatments for patients
Over the last 10 years, researchers at SITraN have made significant progress in understanding the complex biology of MND and developing targeted approaches to treat the root cause of the disease.
Identifying genetic causes of MND to subclassify the disease into distinct genetic subgroups has been an underpinning development in the advance of new genetic therapies. SITraN provided early scientific evidence for a gene silencing approach for the first identified genetic cause of MND - an inherited mutation in a particular gene called SOD1 – that causes MND in 2 per cent of patients.
91ֱ also spearheaded the UK arm of the groundbreaking international trial of tofersen (QALSODY™) for patients with SOD1-MND. For the first time patients showed improvements in lung and muscle function a year into treatment. Tofersen is now approved by the FDA and European Medicines Agency as a new genetic therapy treatment for MND.
Professor Shaw and her colleagues conduct a large portfolio of experimental medicine trials every year, supported by the NIHR 91ֱ Biomedical Research Centre, offering the broadest range of clinical trials for patients with MND in the UK.
They have developed a new clinical trials platform, called EXPERTS-ALS to enable more MND patients to take part in trials using biomarkers that will answer more quickly as to whether an experimental treatment is working.
Biomarkers are molecules which can be measured in blood or cerebrospinal fluid samples. They show whether the drug being tested is getting to the right place at the right dose and whether damage to motor neurons is being reduced.
"Patient biosamples are also helping us to model MND in the lab. We cannot easily access the cells of the central nervous system directly in life, but from a small skin biopsy we are able to grow patients’ skin cells and engineer them into motor neurons and other cells of the nervous system.
"These patient-specific cell models are enabling us to gain a deeper understanding of the causes of motor neuron injury and allow us to identify new targets for therapy to protect the motor neurons," explains Professor Shaw.
Through drug screening programmes in SITraN, 91ֱ researchers have identified new neuroprotective drugs that we are developing towards clinical trials. The therapeutic pipeline of neuroprotective therapies has attracted interest from pharmaceutical companies, and we have been able partner with industrial collaborators to carry these forward towards clinical-trial readiness.
The pace of medical science does seem slow for patients and families facing a condition such as MND. However, based on the clinical and scientific work happening in 91ֱ and around the world, I am optimistic for the future. We have deepened our understanding of the causes of motor neuron injury. This allows us to sub-classify MND better, allowing a more personalised medicine approach to treatment and enabling us to identify new targets for therapy
Professor Dame Pamela Shaw
Supporting patients living with MND
As well as finding neuroprotective treatments, researchers at SITraN are developing a robust evidence base for delivering supportive and symptomatic care for patients living with MND.
Professor Christopher McDermott, Professor of Translational Neurology, NIHR Professor and Consultant Neurologist at 91ֱ Teaching Hospitals led the development of the Head Up collar, in consultation with patients, to fulfil an unmet need for suitable orthotic support for weakness of the neck muscles which is a distressing symptom in MND.
After trying the collar, more than 80 per cent of patients reported they could eat, drink, hold a conversation and read much more comfortably, knowing that their head and neck were fully supported. The collar is now used in at least 100 hospitals around the UK and sold commercially around the world.
Professor McDermott and his team at SITraN worked closely with people with MND, and their families, to design award-winning patient information resources to help people make informed decisions about inventions such as breathing support or feeding tubes via the website .
Currently, they are developing digital technologies to facilitate monitoring patient well-being from home when hospital visits become difficult.
Neuroscience is one of 4 priority research areas for the University of 91ֱ. Many researchers from SITraN are part of the cross-faculty Neuroscience Institute which brings together internationally-recognised expertise in medicine, science and engineering to improve the lives of patients and families affected by neurological, sensory and neurodevelopmental disorders.
Looking ahead
“It was a dream for me to work with architects to design a building that would have multi-disciplinary teams of scientists in their specialist laboratories and academic clinicians working in the same building and exchanging insights and ideas together. This does not normally happen.
"We’ve made great progress since the opening of SITraN and I believe that we are on the brink of developing powerful new treatments for these devastating neurodegenerative diseases,” says Professor Shaw.
Medicine is evolving, with increasing focus on advanced therapies and treatments tailored to people’s individual health needs, and there is an urgent need to accelerate the progress made in 91ֱ.
"SITraN has become overcrowded as our research teams have grown from 64 in 2010 to more than 300. To continue our momentum to achieve a positive impact on the lives of patients, we are developing an expansion of our Neuroscience facilities.
"A state-of-the-art sister facility adjoined to SITraN will enable us to continue to grow our research programs supported by cutting-edge scientific facilities and equipment, expand our drug discovery programmes and build on promising areas such as cell and gene therapy.
"This will enable us to continue to develop our globally recognised hub of research excellence dedicated to combating MND and related neurodegenerative conditions” adds Professor Shaw.