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1st April 2022

Muscles are controlled by nerves to make them move. The nerves that stimulate muscle, together with the muscle fibres to which they are attached, form something called a motor unit.

When motor neurons are lost, the remaining neurons compensate by growing. New branches extend from the remaining motor neurons, to make connections with the muscle fibres which had lost nerve stimulation (innervation). This results in an effective increase in the size of the territory of the motor neuron (motor unit size). In the long term, this is detrimental to the motor neuron, but we really don’t fully understand why.

Motor unit size is known to increase throughout the lifespan of people who have milder forms of SMA. People who receive one of the new treatments for SMA are likely to already have had some motor neuron loss; the remaining motor neurons are going to compensate and exist in a chronically enlarged state.

This scenario is really similar to what is seen after polio infection, where an acute childhood infection causes a loss of motor neurons, inducing compensatory enlargement in the remaining motor neurons. In these individuals, there is a new wave of motor neuron loss in adulthood. There is a very real risk that the same will happen to people who have SMA and have received a drug treatment.

In order to support motor neurons in people living with milder forms of SMA and those who have received treatment, it is vital that we understand what pressures are put upon enlarged motor neurons and find ways to support them.

Dr Lyndsay Murray of the University of Edinburgh has been awarded this four-year scholarship (£113,000) to study ‘Understanding and Supporting motor neurons following compensatory sprouting mouse models’. It aims to:

(1) To perform a screen to test multiple different drugs which should improve motor neuron survival in a mouse model of SMA that has been treated with Spinraza.

(2) To carefully examine motor neurons after they have undergone motor unit enlargement in normal healthy mice, to find out what processes are affected. This work aims to reveal the molecular pathways that are disrupted following chronic enlargement of motor unit size to give us new ideas about how to support them in SMA.

This project may have an important impact on our understanding of SMA, and may help to improve treatment.

This £113,022 scholarship was awarded to this four-year study selected from a number of competing projects submitted to the MDUK / SMA UK joint call for PhD research projects. Selection was by the MDUK Scientific Research Panel with specialist input from clinical and scientific experts in SMA. The process includes input from a lay panel.

The study runs from 2022 – 2026.

Dr Kate Adcock, MDUK’s Director of Research and Innovation, said:

“We are delighted to be working in partnership with SMA UK to fund the study at the University of Edinburgh. Not only will we be funding an excellent study, but we’ll be helping to support a new researcher begin their career in this exciting field.”

Angela Smith-Morgan, CEO of SMA UK echoed this:

"SMA UK are delighted to be working with MDUK to fund this important work. It is an interesting area of research which will add to our understanding of muscle development in people living with SMA."