A cruel disease... and the medical fight to give patients hope where there was none

DAVID Goodall was a gardener who was very fit thanks to a physical, outdoor job. One day, when he was 49, he found that he suddenly couldn’t lift a hedgetrimmer he usually had no problem in manipulating.

Other signs of growing physical weakness quickly followed, but it took visits to his GP and two neurologists plus a battery of tests over 12 months to rule out other possible causes and establish that he was suffering from the incurable degenerative disorder motor neurone disease (MND).

People often have a misconception – probably because the most high profile person associated with MND, Professor Stephen Hawking, has had the disease for 36 years – that it’s usual to live for a long time with it. In fact, most sufferers will survive a few short years. David lost his battle at the age of 54.

The family of four had lost the home that was tied to his job when he could no longer work, and they had to move to a smaller house. His wife also had to leave her job to care for David. But he was able to die peacefully there with his family around him. His daughter Emily credits her dad with leaving his family with “a shared passion for nature and biology that has influenced us all”.

The year after David’s death, Emily took her A-levels and went on to Cardiff University to study Genetics. “Losing my father to MND motivated me to pursue research into MND.” She continued her studies with a PhD at Birmingham University, studying mechanisms that could possibly cause the disease.

She wanted to stay in that field, and wrote a speculative letter to Pamela Shaw, professor of neurology at Sheffield University, who was to become head of the new £18m Sheffield Institute for Transitional Neuroscience (SITraN), the first centre of its kind in Europe, which opened in November 2010.

Emily was appointed to a post-doctoral research post at SITraN and hopes that her work will “play a role in improving the diagnostic process for future families affected by MND, preventing the uncertainty they face and helping them to get the support they need more quickly. It would have made a huge difference to my dad and all of us if we had known much earlier.”

Around five per cent of the 1,200 people diagnosed with MND in the UK each year inherit it through “rogue” genes. The rest have what’s called “sporadic disease”, in that its precise causes are unknown, but are thought to include both predisposition and environmental factors.

At the moment the time it takes to diagnose a case is often nine to 12 months, and the process is hindered by the lack of a simple blood test. This is Emily Goodall’s field of research. Identifying unique markers in the blood would mean early diagnosis. Such a test could also be used regularly to monitor the disease’s progress.

“A year, as it was in Dad’s case, is too long to wait. If we can develop a blood test to use early in the process, then although we still don’t have a cure, the help and support available to patients can be put in place so much earlier – and that is vital.”

As in so many areas of research, the way to new techniques and treatments is being led in some respects by cancer research, which attracts a lot of resources compared to a ‘Cinderella’ area like MND. Although it is a 
dreadful disease, many fewer people suffer from it and breakthroughs have come slowly until recent years.

Emily Goodall is part of a multidisciplinary team of 130 scientists (which will grow to 150) at SITraN, brought together from around the world by Prof Shaw to work very closely on speeding up progress into the causes, treatments and potential cures for MND, the childhood form of the disease (SMA)and related degenerative illnesses such as Parkinson’s disease and Alzheimer’s.

At the moment there is only one treatment for MND, a drug called Riluzole, which slows down the disease’s progress in some patients. Prof Shaw came to Sheffield from Newcastle University in 2000 and her work today involves 50 per cent research and 50 per cent clinical work.

The vision for a dedicated centre for research came to her back in 2006, when a patient who had been a fundraiser travelled to the neurology clinic at Sheffield’s Hallamshire Hospital and said to Shaw: “What would you do with £20m?”

The professor answered: “I would build a dedicated research institute with a multidisciplinary team all focusing on the same thing, working in an environment they enjoy being in.” A further ambition for the dream institute was that it would train the next generation of scientific researchers to work with degenerative neurological disorders.

It took a few years, but the vision was realised because the university, patrons, the people of Sheffield, charities and fundraisers both locally and far away helped to make it happen.

In November 2010 the Queen opened SITraN, and since then the building and its team have become “a magnet”, says the professor. Pathologists, geneticists, cell biologists, neurologists, nurses and a drug screening specialists and others are assembled there to apply their different skills to the same problems. A chance conversation in the corridor can lead to a new collaboration or the solution of a thorny problem, with a scientist in one field teaching a colleague in another field a new technique to try in their work.

Just over two years on from the grand opening of SITraN, what has been achieved?

Research is ongoing to discover how the one rogue gene known to cause the five per cent of MND cases that are genetic is suddenly switched on causing symptoms when a patient reaches a certain age (MND usually strikes aged 40-plus, and nearly twice as many men as women). Sixteen such rogue genes have been identified, and work on these will enable scientists to get a handle on questions around the majority of MND cases, the ‘sporadic’ kind.

Using blood samples provided by local people with the disease, work is being done on every gene in the body to understand how the injury to motor neurones develops, knowledge vital to development of new drug therapies. Advances have been made in care of MND patients with breathing, swallowing and nutritional interventions making their way from lab to clinic rapidly. One new device now being tested is a pacemaker attached to the diaphragm muscles to improve breathing.

Vital work on SMA, led by Professor Mimoun Azzouz, is being done to find a way of ‘switching off’ the SOD1 gene (a faulty gene identified as being involved in causing childhood MND) is advanced and it’s hoped that it will be possible to move from lab to trials of the therapy in humans within two years.

The move from being a group of scientists scattered around one hospital and beyond to a smart, purpose-built building where a great deal of light shines on every problem, and communication between so many great intellects is made easier has attracted interest and funding, says Prof Shaw.

Increasing amounts of research grants, philanthropic donations and industry partnerships have materialised to support its work. MND and SMA have attracted £7.3m in research funding in 18 months.

“MND is one of the so-called ‘orphan’ diseases, but we are now stirring interest from ‘Big Pharma’, so we have funding from AstraZeneca with the Medical Research Council. They are supporting us in how a drug developed for another disease might be used for MND, so we are currently testing it in clinical models. A new trial is about to start on a therapy which acts to improve muscle strength. Several research programmes have improved quality of life for patients.”

These and all the other SITraN projects may lead to new treatments and even a cure in decades to come – too late for current MND patients, perhaps – but the professor says MND research is now gathering pace, She intends to keep at it for as long as she can.

“I’m a glass half full person, and think the disease has to yield to all this effort.”

For information about SITraN or to make a donation go to www.sifoundation.com

Toll of Motor Neurone Disease

MND was first described in 1874, and describes a group of related diseases, affecting the motor nerves or neurones in the brain and spinal cord, which pass messages to the muscles telling them what to do.

MND is a progressive neurodegenerative illness that leads to weakness and wasting of muscles, causing increasing loss of mobility and difficulties with speech, swallowing and breathing.

Some people may experience changes in thinking and behaviour, often referred to as cognitive impairment.

The effects of MND and the rate and pattern of the disease progression vary enormously, as does survival time after diagnosis.

More than 6,000 people in the UK suffer from the disease.