MS usually starts as a relapsing and remitting disease, however, many people go on to develop progressive disease, where symptoms become chronic. Compared to relapsing MS, our understanding of the biological mechanisms underlying progression and disability is far less advanced. This is reflected in the lack of therapies to treat progressive MS, so a greater understanding of the cause of disability is an urgent priority for MS research.
Disability in MS has often been thought to be a direct result of the loss of axons, the long nerve fibres that transmit messages from the brain and spinal cord to other parts of the body. In progressive MS, studies have shown that around 60% of nerve fibres in the spinal cord are lost over 30 years with the disease. This might explain why in progressive MS the signals from the brain, for example, telling the leg to move, are disrupted and lead to symptoms.
However, this loss of nerve fibres as the major cause of disability in MS is at odds with findings in spinal cord injury. In laboratory models of spinal cord injury, as little as 8% of intact nerve fibres in the spinal cord allow the legs to function; and there are case reports in the medical literature of people with an almost completely severed spinal cord who are able to walk with assistance. This suggests that the extent of nerve fibre loss in MS is not large enough to account for disability in MS.
Based on the idea that nerve fibre loss might not be the whole story in MS disability, a recent study published in the Annals of Neurology looked for other possible causes of the reduced transmission of nerve impulses in MS. For this work, led by Professor Klaus Schmierer at the Queen Mary University of London, researchers turned to tissue banks to understand what is happening at the microscopic level in the spinal cord in MS. The study compared spinal cord samples from chronic MS to samples without MS.
Aside from counting nerve fibres, the researchers also examined the electrical connectors or “synapses” between the nerves. When a nerve impulse reaches the end of a nerve, chemical messenger molecules or “neurotransmitters” are released to communicate the signal to the connecting nerve to carry the message on. The researchers measured two proteins involved in this neurotransmitter transfer to detect synapses in the spinal cord.
In an unexpected and exciting finding, the researchers saw that there was extensive loss of synapses in the spinal cord in chronic MS. These were measured by either the size of the synapses, or the quantity of the two synapse proteins in the spinal cord tissue. Compared to nerve cell loss, there was an even greater loss of nerve connectivity (between the remaining nerves) in chronic MS. This is important as the protection or reforming of synapses may provide a completely new treatment development avenue for progressive MS.
This study illustrates the power of directly examining human tissue to advance our understanding of the cause of disability in MS. The MS Research Australia Brain Bank collects post-mortem tissue from people with and without MS for use in research, powering discoveries like this one directly in the human disease. For more information about the MS Research Australia Brain Bank and to register please go to https://msbrainbank.org.au/register-online/ or call 1300 672 265.