BRC-supported researchers have identified a likely cause of damage to the nerves in multiple sclerosis (MS), opening up the possibility of treatments to prevent the disabling symptoms of this neurodegenerative disease.
A team led by Professor David Miller, and funded by the National Institute for Health Research University College London Hospitals BRC and the UK MS Society, used a new MRI technique to reveal the role sodium accumulation plays in nerve cell loss in MS. Results of the study, published this week in the journal BRAIN, showed sodium concentrations in the brain were significantly higher in people with MS compared with people without MS. Sodium accumulation was found especially in progressive MS where there is more disability.
MS is a common chronic disease of the central nervous system affecting 1 in 600 people in the UK. Over the course of several decades, the condition often results in severe neurological disability, including impairment of mobility, sensation, bladder function, vision and cognition.
What happens in MS is the myelin sheath surrounding the nerve fibers become inflamed and damaged. The loss of the myelin sheath – known as demyelination –happens in different areas across the central nervous system. The subsequent loss of nerve cells and fibres (neuroaxonal loss) is what causes long term disability.
The ‘big issue’ in MS is understanding neuroaxonal loss. When a nerve fibre loses its myelin sheath, in an effort to sustain nerve function, there are many additional sodium channels placed along its membrane. This helps conduction as it allows the influx sodium into nerve cells. However, if the increase is prolonged, the cells may take up calcium as a way to extrude the excess sodium, and this may result in cell death.
In the study, Professor Miller and his team used an MRI scanner, which was funded by the MS Society and is dedicated to MS research, to show that detecting the amount of sodium in the brain is a potential new way of predicting damage to nerve fibres, and a tool in developing treatments to prevent that damage.
Professor Miller said: “As the study supports the idea that accumulation of sodium in nerve cells is an important mechanism leading to damage and loss of those cells, it is worth targeting that through treatment trials to try and block accumulation. The treatment potential is that we might be seeing something that is preventable.”
He added: “The NIHR BRC funding was vital to the development of new imaging measures for neuroprotection - imaging measures that provide insight into the causes of neurodegeneration (loss of nerve cells and fibres) and that offer a sensitive means to discover treatments to prevent it.”
Once nerve cells are lost, extracellular space increases, so sodium increases. Hence, new NIHR BRC research, which is being led by Dr Claudia Wheeler-Kingshott, has already began on looking at imaging the intra and extra cellular space separately, to capture the sodium accumulation within the nerve cell, and in the space around the nerve cell.
