Biomedical Sciences

Insights into neuromuscular diseases published in Brain

New discovery reveals insights into both spinal muscular atrophy (SMA) and Charcot-Marie-Tooth disease (CMT)

Many types of neuromuscular disease, such as spinal muscular atrophy (SMA) and Charcot-Marie-Tooth disease (CMT), share similar symptoms. A new study, published by a research team from the University of Edinburgh, working with colleagues at UCL, Dundee University and the University of Cologne, has shown that these similar symptoms are likely caused by overlapping molecular mechanisms.

The study, led by Professor Tom Gillingwater and Dr Ewout Groen, showed that one of the molecular pathways that changes in SMA is the system responsible for recycling unwanted proteins. In spinal muscular atrophy the main disruption to this pathway revolves around a reduction in the levels of one particular protein, called UBA1. The new research revealed that low levels of UBA1 in spinal muscular atrophy affect the function of another key molecular pathway, that is already known to cause Charcot-Marie-Tooth disease (CMT). Specifically, a protein called GARS, which causes Charcot-Marie-Tooth disease type 2D, was found to be affected in spinal muscular atrophy. Importantly, the research team found that therapies which increased levels of UBA1 reversed the problems associated with changes in the GARS protein.

This finding suggests that neuromuscular diseases such as CMT and SMA share common molecular causes, meaning that it may eventually be possible to treat patients with similar drugs.

The study was published in the journal Brain and was funded by the Euan MacDonald Centre, the SMA Trust, the Wellcome Trust and SMA Europe.

Further reading

View full publication on the Brain website (open access)

Prof Tom Gillingwater's lab profile

Dr Ewout Groen's lab profile

The Euan MacDonald Centre website