Repeat Physical Traumas an initiator for motor neuron disease (MND): an insight from professional rugby

Motor Neuron Disease (MND) is a devastating condition affecting neuronal cells responsible for voluntary muscle movement. The risk of developing MND is 1 in 300, predominantly in individuals over 50. Strikingly, this prevalence is 15-fold greater in rugby players, at a significantly younger age-of-onset.

The mechanisms of peripheral neuronal deterioration central to MND are unclear, making treatments elusive. Extracellular vesicles (EVs) are lipid bound vesicles secreted into the extracellular space. Studies have highlighted the critical need of skeletal muscle to produce EVs, where they mediate cell-cell communication, particularly supporting neuronal cells. We have also shown that local and systemic inflammation can alter this communication.

Preliminary studies examining the proteomic profile of plasma-derived EVs from rugby and (non-traumatic) CrossFit individuals of different ages highlighted activation of several degrative cellular responses, including inflammation, with failure in tissue repair/remodelling in rugby players who experienced repetitive traumatic injuries. We hypothesise that the rugby players have exceeded their adaptive and repair mechanisms, comparable to an accelerated ageing process, and that this is driven by chronic, self-proliferative, systemic inflammation, particularly by muscle. 

This PhD aims to expand these findings, examining the origin/production of EVs and using a novel ex-vivo human cell derived 3D nerve-muscle construct will identify the relevance of changes in plasma inflammatory cytokines and EVs on nerve and muscle function. In the longer term, this work will identify much needed targets for interventions to delay/halt the progression of MND in rugby players and the wider MND patient cohort.