In Spinal Muscular Atrophy, Vascular System May Play a Key Role

For the first time, scientists have shown that insufficient blood supply is likely to contribute to motor neuron loss in spinal muscular atrophy (SMA), a finding that potentially opens a new avenue into disease research. The study, entitled “Vascular defects and spinal cord hypoxia in spinal muscular atrophy,” was published in the Annals of Neurology.

The role that the cardiovascular system, and blood vessels in particular, play in SMA pathogenesis is lacking in research; however, cardiac defects have been described in SMA patients as well as in animal models, while disrupted capillary networks have been reported in skeletal muscle from SMA mice.

The team, led by Professor Simon Parson, chair in Anatomy at the University of Aberdeen, with colleagues at Edinburgh, Oxford and University College London, investigated whether defects associated with vasculature play a role in SMA’s motor neuron pathology. The results demonstrated that the capillary bed in the muscle and spinal cord of pre-symptomatic SMA mice was normal, but did not match post-natal development in control littermates. Furthermore, according to the researchers, “during later symptomatic time-points the extent of the vascular architecture in two mouse models of SMA was only around 50% of that observed in control animals.” The team also analyzed skeletal muscle biopsies from human patients, confirming a similar vascular depletion in severe SMA. The findings, the authors write, mean that “vascular defects are a major feature of severe forms of SMA, present in both mouse models and patients, which results in functional hypoxia of motor neurons. As such, abnormal vascular development and resulting hypoxia may contribute to the pathogenesis of SMA.”

The team stressed the importance of research extending beyond the nervous system to include the vascular system. “SMA presents itself like a motor neuron disease so research and treatment has been focussed mainly around protecting motor nerve cells. But, we have shown that in SMA, the blood vessels that course through every structure in the body are also severely affected. Importantly, this results in reduced delivery of oxygen to the body, including the motor nerve cells which die in SMA. This new information provides us with an entirely new avenue for research and the development of potential therapies for this devastating disease,” Professor Parson said in a recent news release.