This article is part of a series of Cure SMA grant announcements that will be shared throughout the next couple of months.

Cure SMA has awarded a $170,000 research grant to Lyndsay Murray, Ph.D., at the University of Edinburgh, for her project titled, “Developing strategies to support enlarged motor units following SMN restoration in mouse models of SMA.”

Dr. Murray and her team note that a significant limitation with existing treatments for SMA is the existence of a clear therapeutic time window, after which administration of treatment results in a significant decrease in therapeutic efficacy. Understanding why treatment after the onset of symptoms is not as efficacious as treatment prior to symptom onset is of critical importance to optimize SMA treatment for all affected individuals. Dr. Murray has shown that a delay in treatment administration correlates with a significant increase of motor unit size. This compensatory enlargement of motor units in SMA may be central to the disease process, yet it is remarkably understudied.

With this grant, Dr. Murray aims to understand the pressures put upon enlarged motor units and develop strategies to support them. In support of this objective, she proposes to perform analysis of enlarged motor units following SMN restoration and investigate whether administration of a widely available antioxidant can offer any protection. Understanding how to support enlarged motor units may lead to novel therapeutic opportunities.

Meet Dr. Murray

Tell us about your work?

I am a researcher based at the University of Edinburgh. I have worked on SMA in labs in the U.K. and Canada since 2006 and started my own lab in Edinburgh in 2014. I use laboratory models of SMA to understand what makes motor neurons vulnerable and aim to develop new ways to protect them.

How did you first become involved with SMA research?

I first became involved in SMA research when I started my Ph.D. in 2006.

What is your current role in SMA research?

We aim to understand what makes motor neurons vulnerable in SMA; that is, why motor neurons get sick and die when there are low levels of SMN protein. This mainly involves using mouse models to work out why motor neurons are dying, and therefore find new ways to protect them.

What do you hope to learn from this research project?

The benefits of current approved therapeutics decrease as disease progresses, and we want to understand why. Using a mouse model of SMA, we have recently shown that when treatment is delayed, motor neuron size increases dramatically. By understanding what happens to these large motor neurons, we can develop strategies to support them.

How will this project work?

We will treat a mouse model of SMA, after its symptoms have started, with a drug like Spinraza. We will then examine what happens to these large motor neurons over time and investigate what aspects of the cells’ activities are disrupted. Also, since previous work has shown that large motor neurons often suffer from heightened levels of stress, we will give a widely available approved supplement that reduce stress and investigate whether this helps motor neurons.

What is the significance of your study?

This work will give insight into why a delay in treatment results in poorer outcomes in individuals affected by SMA, and therefore has the potential to improve outcomes for those treated after symptoms have started.

About Cure SMA’s Basic Research Funding

This grant to Dr. Murray is part of $1,100,000 in new basic research funding that Cure SMA will be announcing over the coming weeks. Basic research is the first step in our comprehensive research model, and we fund basic research to investigate the biology and cause of SMA in order to identify the most effective strategies for drug discovery. We also use this funding to develop tools that facilitate SMA research.