June 11, 2021

expert reaction to study looking at physical exercise as a risk factor for motor neurone disease (MND)

A study published in EBioMedicine looks at physical exercise and development of the neurodegenerative condition motor neurone disease (MND).

Prof Ammar Al-Chalabi, Professor of Neurology and Complex Disease Genetics and Director, King’s College London and Director of King’s MND Care and Research Centre, said:

“This study shows that, particularly in people who already have a genetic tendency to MND, exercise can nudge someone a little closer towards developing MND. The risk is small and far smaller than the benefit of exercise on the risk of heart disease or other conditions, but important for what it tells us about how MND might start.”

Prof Martin Turner, Professor of Clinical Neurology & Neuroscience, University of Oxford, said:

“This study adds to a long-observed but essentially anecdotal observation that those seen in specialised MND clinics frequently report lifelong high levels of physical activity or athleticism. These resonate with occupational risk associations made epidemiologically to professional football, rugby and military service, plus the eponymous baseball player Lou Gehrig (known as The Iron Horse for his physical prowess). However, there is also epidemiological evidence for lower premorbid body mass index in those going on to develop MND, and emerging evidence of a potentially different metabolic profile, including blood lipid differences many years before the onset of symptoms, suggesting a broader set of factors that might overlap with exercise. This type of genetic analysis is powerful but does not yet exclude the interpretation that those developing MND in later life happen to more commonly have the sort of physical or metabolic make-up that then makes them more likely to undertake exercise. It is certainly possible that there are sub-groups of people for who later-life physical over-exertion may be more harmful and contributes one of several ‘hits’ needed to develop MND. This needs more focused study. Importantly however, this study does not show that any increased risk of physical activity in carriers of high-risk genetic variants outweighs the much more solidly established cardiovascular, cancer and mental health benefits of exercise.”

‘Physical exercise is a risk factor for amyotrophic lateral sclerosis: Convergent evidence from Mendelian randomisation, transcriptomics and risk genotypes’ by Thomas H Julian et al. is  published in EBioMedicine.

DOI: https://doi.org/10.1016/j.ebiom.2021.103397

Declared interests

Prof Martin Turner: “I am acknowledged on the Sheffield group’s paper as one of several neurologists contributing patients for their analysis

I have served on the Scientific Advisory Board of Orphazyme and currently sit on the Endpoint Adjudication Committee for Biogen

I have undertaken consultancies for GLG Consulting on the topic of ALS diagnosis, biomarkers and therapy development

I am Commissioning Editor for the Journal of Neurology, Neurosurgery & Psychiatry

I receive funding support from the Motor Neurone Disease Association and My Name’5 Doddie Foundation.”

None others received.