Intense exercise raises MND risk for genetically predisposed people, study finds

A team of researchers at the University of Sheffield has confirmed something long suspected but never definitively proven: for people born with certain genetic variations, pushing hard through intense exercise may accelerate the onset of motor neurone disease. The finding, published in EBioMedicine, represents a shift in how scientists understand the relationship between physical exertion and this devastating neurological condition.

Motor neurone disease affects roughly 5,000 people across the UK at any given time. The illness progressively damages the nerves that control movement, gradually severing the connection between brain and muscle. As the disease advances, people lose the ability to move their limbs, speak clearly, swallow, and eventually breathe without assistance. The lifetime risk for the general population sits at about one in 400—a low but real possibility. Yet among professional athletes, particularly football players, the risk climbs to six times that baseline, a disparity that has puzzled researchers for years.

Dr. Johnathan Cooper-Knoc, a neurologist at Sheffield, noted that while exercise had long been suspected as a contributing factor, the link remained contentious in scientific circles. "This study confirms that in some people, frequent strenuous exercise leads to an increase in the risk of MND," he said. The research team analyzed data from the UK Biobank, a vast repository holding genetic information and lifestyle details on half a million individuals. By examining which people carried genetic markers associated with both a tendency toward vigorous exercise and susceptibility to motor neurone disease, the researchers traced a causal pathway: genetic predisposition plus intense physical activity equals elevated disease risk.

The mechanism appears to involve how strenuous activity alters the expression of genes already linked to the condition. Among people carrying a specific mutation responsible for roughly 10 percent of all MND cases, those who engaged in regular high-intensity exercise developed the disease earlier than their sedentary counterparts. The finding does not mean exercise causes motor neurone disease in most people—the vast majority of athletes and fitness enthusiasts never develop it. Rather, it suggests that for a small subset of the population, the combination of genetic vulnerability and physical stress creates conditions where the disease emerges sooner.

Professor Dame Pamela Shaw, director of the Neuroscience Institute at Sheffield, emphasized the narrowness of the at-risk group while pointing toward the next phase of investigation. "Clearly, most people who undertake strenuous exercise do not develop motor neurone injury and more work is needed to pin-point the precise genetic risk factors involved," she said. The team's immediate goal is to develop tests capable of identifying which individuals carry the dangerous genetic combination, allowing them to make informed choices about their exercise habits. The longer-term aim is to map the full landscape of environmental and genetic factors that trigger the disease, ultimately enabling prevention strategies tailored to those most vulnerable.

The disease itself remains poorly understood. About one in ten cases run in families, inherited through a single faulty gene. The remaining 90 percent arise from a complex interplay between multiple genetic factors and environmental triggers—a puzzle that researchers are only beginning to solve. High-profile athletes have brought the condition into public view in recent years: rugby league player Rob Burrow, rugby union's Doddie Weir, and footballer Stephen Darby have all spoken publicly about their diagnoses, lending urgency to the search for answers. This latest research suggests that for some of them, the very activity that defined their careers may have hastened the disease's arrival.