At some point in an MND patient’s life, their motor neurones start to die, leading to muscle wasting and eventually death – typically within two years of diagnosis.

Disruption in the ability of central nervous system to create energy is thought to be a major contributing factor and could influence disease progression rates.

But scientists in Sheffield have discovered an intervention that could potentially accelerate energy production in the central nervous system and encourage brain cells to better support motor neurones, thus limiting the disease’s progression.

They converted skin cells into brain cells called astrocytes – star-shaped brain cells that play a key role in supporting motor neurones by acting as a crucial source of energy in the central nervous system.

They then compared the energy metabolism of cells taken from MND patients versus healthy controls. This was made possible using new “metabolic phenotyping” technology developed by Biolog, Inc, a Californian biotech company.

As a result, the University of Sheffield’s Institute for Translational Neuroscience (SITraN) researchers discovered the loss of a key enzyme that could have major consequences for how the central nervous system copes with ageing, stress and loss of energy metabolism.

Working in collaboration with Biolog, Inc., they sought differences in the metabolism of astrocytes from MND patients.

Dr Allen, a Motor Neurone Disease Association-funded senior researcher, found that cells from MND patients had reduced ability to turn a metabolic substrate called adenosine into energy due to loss of an enzyme called adenosine deaminase.

The consequence of this loss could be a toxic build-up of adenosine in the central nervous system and subsequent loss of inosine production, a metabolic intermediate that is generally protective.

Until now, the link between MND and inosine production through the loss of adenosine deaminase had not been made. When Dr Allen fed the brain astrocytes inosine, energy production increased and the patient’s astrocytes became more supportive towards motor neurones, helping them to live longer.

Dr Allen says: “We are really excited about this set of results as no one has implicated adenosine deaminase in MND before.

“Our results indicate that the higher the level of adenosine deaminase, the greater the protection against adenosine mediated toxicity and the greater support towards motor neurones when given inosine.

“Although we are at an early stage, I think increasing adenosine deaminase levels, combined with inosine supplementation has the potential to slow down disease progression in MND patients. But a lot of further testing in the laboratory has to be performed.”

Altering the level of adenosine deaminase by gene therapy has previously been shown to be beneficial and safe in patients suffering from severe combined immunodeficiency disease.

Inosine is a safe and readily-available nutritional supplement, which has been successfully tested in Parkinson’s disease patients. There is therefore hope that, in the future, this combination of treatment could work in people with MND, improving their quality of life and helping them live longer.

Meanwhile, a separate study has raised the prospect that statins could help to protect against MND.

It stems from the discovery that high cholesterol could be a possible risk factor for the development of motor neurone disease (MND).

This is according to a large study of genetic data led in the UK by Queen Mary University of London, in collaboration with the National Institutes of Health in the US.

The results suggest that cholesterol-lowering drugs, such as statins, could be used to prevent the onset of MND, if confirmed in clinical trials.

Dr Alastair Noyce, from Queen Mary’s Wolfson Institute of Preventive Medicine, say: “This is the largest study to-date looking at causal risk factors for motor neurone disease and we saw that higher levels of LDL cholesterol were causally linked with a greater risk of the disease.

“We have well-established drugs that can lower cholesterol and we should look into whether they could protect against this terrible disease, which currently has no cure.

“The next steps will include studying whether lowering levels of cholesterol might have a protective effect against MND, and potentially evaluating the use of cholesterol-modifying drugs in people at risk of MND.”

Published in the journal Annals of Neurology, the team searched genetic datasets of around 25 million people (including more than 337,000 people from the UK Biobank) to find risk factors for developing MND.

While the datasets did not contain data on individuals’ actual cholesterol levels, the team studied genetic markers that are linked to cholesterol levels, and are more likely to suggest a causal link with risk of MND rather than simply associations, which are usually reported from observational studies.

A randomised control trial would be the definitive proof to confirm any causal link and the ability of statins to prevent MND.

In addition to the causal effect of high cholesterol, they also found genetic associations with smoking behaviour and lower levels of educational achievement, and an increased risk of MND.

While low levels of exercise were associated with a protective effect, more aggressive exercise was associated with increased risk. However, of these findings, only high cholesterol emerged as a clear modifiable factor that could be targeted to reduce risk of MND.

The research was carried out at Queen Mary’s Preventive Neurology Unit, which has been funded by Barts Charity.