Everything you need to know about motor neurone disease

It’s the diagnosis that everyone dreads. Motor neurone disease (MND) is a progressive and, as yet, incurable illness that results in gradual paralysis and death, almost certainly within one to five years. It causes the degeneration of nerve cells, known as motor neurones, which run from the spinal cord to the brain, controlling muscle movement.

The most famous sufferer was probably the late Prof Stephen Hawking, who was a highly unusual case as he lived for 55 years with the disease.

With one in 300 people at risk of MND in their lifetime, what causes it and what are the future hopes for treatment?

Jump to:

• Is ALS the same as MND?
• What are the first signs of MND?
• How is MND diagnosed?
• What are the symptoms of ALS?
• Is MND hereditary?
• What causes MND? 
• Are former athletes more at risk?
• What is the life expectancy of someone living with ALS?
• What treatments are available and what’s coming in the future?

Is ALS the same as MND?

The term MND encompasses a range of neurological conditions, including ALS (amyotrophic lateral sclerosis), which is the most severe. ALS affects both the upper motor neurones that travel from the brain to the spinal cord and the lower motor neurones, which branch out to the various muscle groups around the body.

Primary lateral sclerosis, where patients experience growing weakness in their muscle movement, is not quite as debilitating as the muscles do not waste away, and patients can live for up to 20 years.

Pseudobulbar palsy and progressive bulbar palsy can affect the tongue, facial movements and speech. In both cases, the life expectancy depends heavily on whether the disease progresses to full-blown ALS.

What are the first signs of MND?

Symptoms can include the following, says Dr Nicholas Cole, the head of research at the MND Association:  

• Muscle cramps
• Spasms
• Weakness or stiffness in the legs, feet, arms or hands
• Swallowing difficulties
• Slurred speech
• Breathing problems

“Some people experience what is referred to as ‘foot drop’, which can cause them to trip or fall,” says Dr Cole. 

“We heard of people being accused of being drunk because they struggle to pronounce certain words.”

It’s important to note that the majority of people with these symptoms do not have MND. Muscle spasms, for example, can be a result of dehydration or sitting for long periods of time.

How is MND diagnosed?

Diagnosing MND is a long and complex process. If a GP suspects you have early symptoms, they will refer you to a neurologist.

Reaching a diagnosis typically requires a combination of MRI scans and electromyography, which is a method of detecting the electrical activity of muscle fibres. Doctors will also conduct tests to measure the electrical activity of the nerves, as well as blood and urine tests to rule out other diseases.

Patients can initially sometimes be mistakenly diagnosed with stroke, carpal tunnel syndrome or pinched nerves.

However, new research suggests that the earliest signs of the disease may be present years, or even decades, before symptoms develop. A study by scientists in Scotland found that toxic proteins that contribute to the death of motor neurones in the brain could be identified in the gut, skin and lymph nodes up to 14 years before diagnosis.

In future, it is hoped that this information could be used to diagnose patients at a much earlier stage, which would give therapies a better chance of succeeding.

What are the symptoms of ALS?

The most recognisable symptoms are:

• Muscle wasting and atrophy due to the lack of signalling from the brain, meaning that most patients ultimately become unable to stand or walk and experience difficulties speaking and swallowing.
• Breathing problems are also common as the disease affects the muscles in the chest wall, with patients becoming dependent on either breathing masks or a ventilator.
• About half of patients experience problems with language and decision making, with some developing a form of dementia as their disease progresses.

Is MND hereditary?

Inherited MND affects a minority of people – up to one in 10, according to the Motor Neurone Disease Association. Where this is the case, the charity said it is impossible to predict when or if a family history means MND will occur and other triggers may still be needed for the disease to take hold.

What causes MND? 

MND can strike at any age, but most patients are aged between 55 and 75. While rogue gene mutations are thought to play a role in about 10 per cent of cases, the precise triggers for MND remain a mystery.

Isaac Chiu, an associate professor at Harvard Medical School, says: “The majority of cases occur without an obvious cause. It is not yet clear what environmental risk factors could cause the disease, though there has been speculation.”

Military veterans have been found to be more likely to develop MND, with some suggesting this is linked to greater exposure to lead, pesticides and other toxins.

Another theory is that either genetic or environmental factors trigger a form of immune system dysfunction, which contributes to the death of motor neurones, perhaps mediated by other brain cells.

There has been progress in understanding how this might happen. In March 2023, Harvard researchers published a paper, in the journal Neuron, which linked the death of motor neurones to an inflammatory process driven by a protein called gasdermin E, which is expressed in large quantities in motor neurones.

“Gasdermin E is stimulated by both neurotoxins and other ALS-associated proteins, and it then damages structures called mitochondria, which are the powerhouses of neurones,” reports Dr Chiu. “This causes degeneration.”

Dr Chiu and his colleagues were hopeful that this could represent a new treatment target for MND, but the research is still very much in the early stages and has not reached human trials.

Are former athletes more at risk?

Doddie Weir, the Scottish rugby union legend, died last November following a five-year battle with MND, while Rob Burrow, the former Leeds Rhinos rugby league star, died in June 2024.

In 2018, Stephen Darby, the ex-Bradford City defender, was told he had the disease at the age of 29, just months after marrying Steph Houghton, the former Lionesses captain.

But while researchers have theorised that brain traumas experienced during contact sports could increase the risk of developing MND, the link between sport and the disease remains inconclusive.

“We are co-founding a research project which is looking to investigate whether traumatic head injuries can increase the risk of developing MND,” says Dr Cole. “It is hoped that this may identify factors or strategies that could potentially lower the risk.”

What is the life expectancy of someone living with ALS?

While the prognosis for newly diagnosed patients is bleak, with most dying within a few years, 10 per cent of people with the disease live for a decade or more.

Prof Hawking lived with MND for over half a century after being diagnosed at the age of 21. People who develop the condition at a young age tend to live for much longer for reasons that are unknown, although his wealth and fame also meant that he benefited from exceptional medical care to help mitigate risks such as choking and pneumonia.

“I have had motor neurone disease for practically all my adult life,” Prof Hawking once told The BMJ. 

“Yet it has not prevented me from having a very attractive family and being successful in my work. I have been lucky that my condition has progressed more slowly than is often the case. But it shows that one need not lose hope.”

What treatments are available and what’s coming in the future?

Right now, the only medication licensed in the UK is an oral tablet called riluzole. The drug has been shown, in clinical trials, to increase life expectancy by a few months. 

It temporarily reduces damage to motor neurones by decreasing levels of a brain chemical called glutamate, which transports messages from other nerve cells to motor neurones. 

However, it can have side effects such as dizziness, raised heart rate and bladder pain.

But more hope is on the horizon. In early 2023, the US Food and Drug Administration approved a drug called tofersen, which is designed specifically for MND patients with a mutation in the SOD1 gene, about 2 per cent of all MND cases. This gene defect causes a faulty SOD1 protein to be made, which is toxic to motor neurones.

Dr Cole explains: “Tofersen is an antisense oligonucleotide, which means that it has been specifically designed to target the mistake in the SOD1 gene. It stops the faulty protein from being made.”

The UK currently has an early access programme to enable patients with so-called SOD1 MND to gain access to tofersen without needing to wait for approval by UK regulators.

Other approaches are currently being trialled which scientists hope could be used to slow down and perhaps even reverse symptoms in a much larger population of patients. 

In the UK, Europe and Australia, scientists are investigating an unusual idea for how the disease develops.

“One potential treatment, which initially sounds a little bit leftfield, comes from the theory that MND is caused by the activation of ancient viruses known as retroviruses which are hidden within our DNA,” notes Dr Cole.

“A trial called Lighthouse II is underway to test whether Triumeq, which is approved to treat HIV, is beneficial for people living with MND.”