It is a terrifying, rapidly fatal condition that destroys the nerves in the brain and spinal cord, robbing sufferers of their ability to move, eat and eventually breathe.
Motor neurone disease – known as MND – affects 5,000 adults in the UK at any one time, with about 1,100 diagnosed each year. The numbers seem to be rising steadily – and, crucially, it has no cure.
While ageing is the biggest single risk factor – the majority of people are diagnosed between 50 and 70 – scientists believe that MND does not have just one single cause.
The disease, which damages the motor neurones – the nerve cells responsible for controlling movement – is grouped into two categories: familial, meaning it is inherited and accounting for around one in ten cases, and sporadic, where it occurs in people with no known family history.
Many scientists now believe the latter cases are triggered by a complex interaction between genes, lifestyle and environmental exposures.
A string of high-profile diagnoses among elite athletes, including rugby stars Rob Burrow and Lewis Moody and former England cricketer David Lawrence, has fuelled questions why healthy young men in peak physical fitness seem increasingly to be struck down.
The most famous sufferer was physicist Stephen Hawking, who was diagnosed with a form of MND in 1963, aged just 21.
Doctors initially gave him only a few years to live, but he survived for more than five decades – becoming one of the world’s most recognisable scientists.
Professor Ammar Al-Chalabi, of King’s College London, who set up the MND Register to identify potential environmental triggers that may interact with a person’s genes to cause the disease, believes there could be more cases linked to lifestyle factors than experts previously thought.
‘MND isn’t all genes and it isn’t all lifestyle,’ he says. ‘Roughly half your risk comes from your genes, and about half comes from how you live and what you’re exposed to, with some contribution down to ageing and biological chance.
Physicist Stephen Hawking, who was diagnosed with a form of motor neurone disease in 1963, aged just 21
‘We don’t yet know exactly which lifestyle factors matter, but it would be surprising if lifestyle didn’t play a significant role at all.’
PROFESSOR Al-Chalabi believes the challenge facing researchers is that no single risk factor appears to fully explain the disease.
Instead, he says MND is likely to emerge when a range of them accumulate over a lifetime in somebody already genetically susceptible. As well as smoking, exposure to certain pesticides, pollution and, more surprisingly, extremely strenuous physical activity have all been linked to increased risk.
Professor Dame Pamela Shaw, a leading MND researcher, says: ‘What’s always struck me in clinic is that most of my MND patients are slim and active. You very rarely see it in people who’ve led a really sedentary life.’
This led her to investigate a possible link between exercise and MND. One study, co-authored by Professor Shaw and published in the journal EBioMedicine, found that ‘frequent strenuous exercise’ – at least six hours of intensive physical activity or 12 hours of more moderate activity a week – increased the risk of MND in those who carried genetic variants that predisposed them to the disease.
They suggested low levels of oxygen in the body during strenuous exercise could be leading to a process called oxidative stress in the motor neurones – this may lead to damage and eventually cause the cells to die.
In separate research, Professor Shaw and her team found that in people genetically predisposed to MND, those who exercised more intensely tended to develop symptoms at a younger age. The findings echoed those of a study of competitors in the gruelling 90km (56-mile) Vasaloppet cross- country ski race.
Swedish researchers found the fastest skiers, those at the very top of the performance spectrum, were four times more likely to develop MND than the general population. But competitors who finished in the middle of the pack had a lower-than-average risk.
It suggests the increased risk, if it exists, may be confined to people participating in the highest levels of physical activity. Professor Shaw believes such a risk is likely to stem from repeatedly pushing the motor system to its limits rather than from normal recreational exercise.
She says: ‘Most athletes will never develop MND. What our work suggests is that in a small number of people with the wrong genes, years of very intense exercise may bring the disease to the surface earlier.
‘The ultimate goal isn’t to blame exercise. It’s to understand the biology well enough that we can give sensible lifestyle advice and, crucially, develop ways to prevent MND in people we know are at higher risk.’
Smoking has been heavily investigated as a possible trigger for MND. Some studies suggest those who have ever smoked may be 20 to 40 per cent more likely to develop it than those who have never smoked, although scientists stress the evidence remains mixed. Research indicates that smokers diagnosed with MND typically experience the onset of symptoms at a younger age than non-smokers. Some studies have suggested women who smoke may face a particularly elevated risk, especially after the menopause.
Several high-profile rugby players, including Rob Burrow, have been diagnosed with MND, prompting research into whether playing the sport could influence the risk
Burrow pictured in 2021. Many scientists now believe the latter cases are triggered by a complex interaction between genes, lifestyle and environmental exposures
But these studies do not pinpoint an exact number of cigarettes that increase the risk, the age at which starting smoking has the highest risk or the impact of vaping.
What is known for sure is that smoking causes irreversible harm to nearly every organ in the body, primarily driven by inhaled tar, nicotine and carbon monoxide.
Scientists believe tobacco smoke could contribute to MND by increasing inflammation and oxidative stress throughout the body, while also exposing nerve cells to potentially harmful chemicals.
In addition, quitting smoking does offer clear benefits to those living with MND. Because the disease affects the muscles involved in breathing, avoiding the additional strain of smoking may help reduce the risk of chest infections and respiratory complications.
While no specific food has been proven to cause MND, some diets have been linked to an increased risk of cell damage and inflammation. One US study found people with the highest mercury exposure, often through consuming large predatory fish such as swordfish and shark, were twice as likely to have MND.
Experts stress this remains only a possible contributor and any increase in risk is probably small.
SWORDFISH and shark contain particularly high levels of mercury because they sit at the top of the food chain, feeding on smaller fish that accumulate the toxic metal.
The NHS advises adults to eat no more than one portion of either each week, while children and pregnant women are advised to avoid them altogether. Expectant mothers are also advised to limit tuna because it contains more mercury than most other fish.
A more unusual theory involves a poisonous wild mushroom known as the false morel. Interest in the fungus was heightened by research into an apparent cluster of MND cases in the French Alpine village of Montchavin in 2021.
All 14 patients found to have the disease had eaten the mushrooms, while unaffected locals had not.
False morels contain a toxin called gyromitrin, which is converted in the body into a chemical capable of damaging nerve cells.
Some scientists have suggested repeated exposure could contribute to MND developing years later. However, experts stress the findings do not prove cause and effect, and there is currently no solid evidence that false morel poisoning causes MND.
Lack of Vitamin D has also been investigated because deficiency is common in a number of neurodegenerative conditions, including MND. The vitamin plays an important role in muscle function, inflammation control and immune health, and some studies have suggested low levels may be linked to faster disease progression.
Researchers have also explored whether geography may offer clues. Scotland has historically recorded slightly higher rates of MND than other parts of the UK, leading to suggestions that lower levels of sunlight and vitamin D production could play a role.
Similar theories have been examined in northern US states, where people receive less year-round sunshine. However, experts caution that there is little evidence that vitamin D deficiency directly increases a person’s risk of developing MND.
While maintaining healthy vitamin D levels is important for overall health, scientists have yet to establish a clear causal link with the disease. Dr Eva Feldman, director of the ALS Centre of Excellence at the University of Michigan, said studies have not shown that people living in northern regions of the US are at greater risk of MND.
Another theory is that prolonged exposure to certain environmental toxins and chemicals such as agricultural chemicals, pesticides, heavy metals and industrial solvents may increase the risk.
Several studies found that farmers, agricultural workers and others who regularly handle pesticides appear to be at greater risk of developing MND than the general population.
Researchers believe long-term exposure to certain insecticides, fungicides and fumigants may play a role, although they stress the evidence shows an association rather than proving the chemicals cause the disease.
The strongest evidence relates to people with years of occupational exposure, such as farmers and pesticide applicators.
Researchers have repeatedly linked these workers to a higher risk of MND, particularly after exposure to older pesticides that can persist in the body for years – although many have since been banned or heavily restricted.
Commenting on the study, Dr Belinda Cupid, head of research at the MND Association, said: ‘The evidence that exposure to pesticides is a contributory risk factor towards getting MND is stacking up and I’m sure will be the focus of future research.’
Back in the US, Dr Feldman is currently leading an extensive 30-year study that is following thousands of workers based in northern Michigan – one of the states with the nation’s highest MND death rates – to investigate whether pollution can help explain the disease.
She said the state’s automotive industry and extensive cherry farming could expose residents to heavy metals and pesticides – two of the environmental factors researchers are investigating as possible contributors to MND.
However Professor Kevin Talbot, a clinician scientist with 25 years of experience in diagnosing and managing MND and related diseases, warns against jumping to any conclusions about toxins or some new environmental poison to explain the rising numbers of sufferers.
‘There’s no solid evidence that heavy metals, pesticides or other toxins cause motor neurone disease,’ says Professor Talbot, who set up the MND Register with Professor Al-Chalabi.
‘If the environment is involved, it’s acting on people who are already genetically susceptible, and we need rigorous, unbiased science to prove it.’
