Page last updated: 17th December 2015

New research from the laboratory of Simon Parson (University of Aberdeen) and collaborators in London and Oxford indicates that a faulty blood supply may play an important role in the death of motor neurons seen in spinal muscular atrophy.

SMA was originally believed to be a disease that only affects the motor nerves, which are the cells that connect the brain and spinal cord with our muscles. However, over the last few years, increasing evidence suggests that other cells and tissues may be affected by the low levels of survival motor neuron (SMN) protein that cause the disease (click here for more information).

This has significant consequences for SMA therapy development, as drugs will likely need to target numerous different cell and tissue types in order to have the greatest chance of success. It is therefore important that we understand how low SMN protein levels affect the different systems of the body.

Prof. Parson works on blood vessels (which form the vascular system) of SMA mice. His laboratory has previously shown that the structure of capillaries, which are the smallest blood vessels found in the body (Figure 1), is severely affected in the muscles of SMA mice.

It was hypothesised that these defects would disturb the delivery of oxygen to SMA muscles, and therefore reduce their ability to work properly. However, this theory was not tested.

Figure 1. The vasculature system. Oxygenated blood travels away from the lungs, through arteries and then arterioles, until it reaches the capillaries. Capillaries are the smallest blood vessels in the body and they allow the exchange of various useful (e.g. oxygen) and waste products (e.g. carbon dioxide) between blood and cells. Once oxygen has been delivered to the cells, deoxygenated blood can be carried back to the lungs via the heart along venules followed by veins.

The latest work published by the Parson Laboratory makes use of a technique able to measure the amount of useful oxygen in different mouse tissues. The research indicates that the blood vessel defects observed in SMA do indeed affect how well the vascular system functions. The reduced density and diameter of SMA muscle capillaries increases the distance that oxygen has to travel, resulting in low oxygen levels in areas that need it.

The defects in blood vessel structure were also shown to be present in the muscles of severe SMA patients.

The vascular system is also severely affected in the spinal cord of SMA mice. This results in a lack of oxygen being delivered to the nerve cells found within the spinal cord, such as the motor neurons. It is believed that this failure to deliver the required oxygen to the nervous system may contribute to the death of the motor neurons.

This work indicates that defects in the vascular system of muscles and the spinal cord are a feature of SMA. These flaws affect the amount of oxygen transported to the tissues, which has profound effects on their ability to function correctly. This research from the Parson Laboratory emphasises the importance of understanding how low levels of SMN protein affect the body as a whole, and not just the nervous system.