Protecting motor neurones in spinal muscular atrophy

Prof Thomas Gillingwater

This project by Professor Tom Gillingwater at Edinburgh University is based on the observation that in mice with spinal muscular atrophy (SMA), some populations of motor neurones survive whereas others are lost. The biological mechanisms underlying this are not well understood and this research will test the theory that changes in the activity of particular genes underlie this selective preservation. Understanding this survival mechanism could highlight new targets for future therapies; it may be possible to use pharmacological or genetic techniques to reproduce this protective effect in vulnerable motor neurones in people with SMA and related conditions.

Update 12/12/17: New research into the role of SMN protein – new study from Prof Gillingwater and colleagues

Update 16/6/17: Improving energy production could protect motor neurons from SMA – study from Prof Gillingwater and colleagues

This project is co-funded by Muscular Dystrophy UK and The SMA Trust – a collaborative partnership established to accelerate progress in the search for treatments and eventually cures for spinal muscular atrophy.

What are the researchers aiming to do in this project?

Spinal muscular atrophy (SMA) is caused by deterioration of motor neurones (the nerves that connect the spinal cord to muscle), but certain populations of motor neurones escape this fate. The selective protection of some populations of motor neurones does not seem to be linked to their location or size, as pools of survival and vulnerable motor neurones are found in very close proximity to one another (1mm).

Preliminary work from Professor Gillingwater’s group has shown that in the protected motor neurones, certain genes are turned on or off, suggesting that gene activity plays a role in protection. The aim of this project is to identify the specific genes and pathways involved in this protection, as they could be useful therapeutic targets.

To test this idea, gene activity in different populations of motor neurones in mice with and without SMA will be measured. Genes that are found to have different activities in protected motor neurones, compared to vulnerable ones, and whose activity is altered in SMA, could be promoting survival. These pro-survival genes will be further studied in a zebrafish model of SMA; this model allows changes in gene activity to be made easily using genetic or pharmacological techniques. The zebrafish genes will be manipulated to mimic the ‘pro-survival’ changes in gene expression to see if this has a positive impact on the symptoms.

How will the outcomes of the research benefit patients?

Understanding why some motor neurones are particularly resilient in SMA, when others are lost, will provide fundamental biological insights into the mechanisms of SMA, but will also identify critical features of protected motor neurones that protect them from degeneration. This may highlight attractive therapeutic targets for ensuring ‘survival’ characteristics in all motor neurones in SMA; it may be possible to use pharmacological or genetic techniques to reproduce this protective effect in vulnerable motor neurones in people with SMA and related conditions.

Grant information

Project leader: Professor Tom Gillingwater
Location: Edinburgh University
Conditions: Spinal muscular atrophy
Duration: two years, starting 2014
Total project cost: £118,000
Official title: Identifying and protecting vulnerable motor neurones in spinal muscular atrophy (SMA)

Further information and links

Download a summary of this research project

Learn more about spinal muscular atrophy

Read about other spinal muscular atrophy research projects we are funding

Read the latest research news for spinal muscular atrophy

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