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Spinal muscular atrophy (SMA) research at the Euan MacDonald Centre is a vibrant and multi-laboratory effort to understand and treat this devastating childhood form of motor neuron disease, bringing together basic science, disease modelling, and therapeutic discovery.
SMA – spinal muscular atrophy is a rare inherited genetic condition affecting approximately 1 in 10,000 births. Around 1 in 55-60 people are carriers. If two people with the gene have a baby, there is a one in four chance of that child inheriting SMA. The disease progresses very quickly and is so rare that a GP, midwife, or health visitor might never see a child with SMA in their whole career.
SMA is a trail blazer amid neurodegenerative diseases, having 3 approved treatments. All of them aim to target the underlying genetic problem in SMA, and each can be remarkably effective when given at an early stage. Despite the incredible successes in the SMA field, people can still experience ongoing weakness after treatment which can lead to lasting disability. This is particularly true for those with the most severe form of the disease and for those where treatment has been delayed. This highlights the need for continued research into this devastating disorder.
SMA has turned out to be even more complex than was imagined, with unexpected outcomes both with and without therapy. Scientists investigating this condition all strive to understand SMA more completely and how it should be treated, toward ensuring long and healthy lives for those affected by spinal muscular atrophy (SMA).
Profs Gillingwater and Parson have been prominent in the public campaign to introduce routine newborn screening for SMA. At present the UK routinely screens for conditions such as cystic fibrosis, and congenital hypothyroidism, but not SMA. This spring, Scotland will become the first country in the UK to begin national screening for Spinal Muscular Atrophy (SMA), which affects movement, breathing and swallowing. Early screening could lead to earlier treatment before symptoms start and lead to better health outcomes for children born with SMA.
Current research
Three Principal Investigators at the forefront of SMA research in Scotland are Prof Tom Gillingwater – University of Edinburgh, Dr Lyndsay Murray – University of Edinburgh, and Prof Simon Parson – University of Aberdeen.
Professor Tom Gillingwater leads research into the cellular and molecular mechanisms underpinning SMA, including gene- and drug-based approaches to protect motor neurons and explore novel therapies such as gene therapy for rare forms like X-linked SMA, supported by new competitive funding and advanced animal models.
Recently, Prof Gillingwater’s lab has been focusing on understanding how and why early changes, occurring even before birth, can affect normal brain development in a subset of children who have the most severe form of SMA. They have been exploring ways in which existing SMA therapies can be better optimized to address these wider issues.
Dr Lyndsay Murray leads investigations into how motor neurons respond to the drugs which are approved for use in people with SMA and better understand the problems which remain after treatment. She is particularly interested in looking at the connections between the neurons and muscle and the extent to which these are repaired after therapies are given. Her goal is to find ways to improve the efficacy of currently approved therapies and identify new add-on therapies which can complement existing approaches.
Dr Murray and her team have been studying mice which have been genetically modified to recapitulate SMA. They have found that when the mice are given the approved drugs at a very early stage in the disease, the connections between muscle and nerve can be restored. However, when treatment is delayed, even by just 1 day, the connections cannot repair as efficiently. The team is trialing a range of strategies to bolster the repair of these connections. As part of this effort, they were recently awarded £270K in new funding from the USA based charity, the SMA Foundation, to better understand how neurons and muscles interact during repair, and what limits the capacity for repair in SMA.
Professor Simon Parson leads investigations to understand how many other cells, tissues, and organs as well as motor neurons are affected in SMA. He is especially interested in the blood vessels that supply every part of the body. He has developed a new mouse model to study this and is also using SMA model human blood vessel cells in culture. These studies will help to understand if current therapies can target non-motor neuronal pathology. They will also help us to understand how blood vessel abnormalities and organ pathology contribute to disease and reveal new targets for intervention.
Prof Parson and his team have recently described important damage to the barrier which separates blood from the nervous system in SMA patients. This leads to leakage and is a direct route for blood vessel damage to impact motor neuron survival. Current work aims to understand this and explore potential therapies.
SMA funding
Lyndsay’s team is currently funded by a range of charities including Motor Neuron Disease Scotland, the Anatomical Society, Cure SMA, the SMA Foundation and Muscular Dystrophy UK.
Tom’s team’s research has been generously supported by a range of funders, including the Euan MacDonald Centre, Muscular Dystrophy UK (MDUK), SMA Europe, MND Scotland, LifeArc, AFM, My Name’s Doddie Foundation, and the EU Horizon 2020 Programme.
Simon’s team are funded by SMA Europe, Anatomical Society, Tenovus Scotland and Grampian Endowments.
Relevant links
Prof Tom Gillingwater profile
Dr Lyndsay Murray profile
Prof Simon Parson profile
Scottish Government SMA screening pilot test announcement
NHS UK information page about SMA
For support and information about SMA please visit the SMA UK website
Support the Euan MacDonald Centre
Relevant academic papers
Image created with Canva