SMA Trust-funded researchers have found that improving energy production in certain motor neurons with SMA could potentially protect them from damage. This could lead to the development of new treatments.
What were the researchers aiming to find out?
SMA is a condition affecting motor neurons (the nerves that connect the spinal cord to muscle), causing them to deteriorate and eventually die. There are certain groups of motor neurons that escape this fate, though the reasons behind this are not clear.
With support from Muscular Dystrophy UK and The SMA Trust, Professor Tom Gillingwater and Professor Catherina Becker and their colleagues at Edinburgh University investigated why some motor neurons are protected and some aren’t.
Previous research from Professor Gillingwater’s group had shown that in protected motor neurons, certain genes are turned on or off, suggesting that gene activity plays a role in protection. The aim of this project was to identify the specific genes and pathways involved in this protection, as they could be useful therapeutic targets.
What did they find out?
Professor Gillingwater and his team compared the gene activity of the different motor neuron populations in mouse models with SMA. They found that genes involved with energy production were more active in protected motor neurons than in vulnerable ones. This meant that the protected neurons were more efficient at generating energy.
The team then investigated whether it might be possible to protect vulnerable motor neurons by improving their energy production. They treated a zebrafish model of SMA with an FDA-approved drug called terazosin, which activates a specific gene involved in energy production. Terazosin reduced the number of damaged motor neurons in this zebrafish model, suggesting that it has a protective effect.
How might this help people living with SMA?
These findings improve our understanding of the underlying biology of SMA, which is key to developing effective treatments. Although there is now a licensed treatment that addresses the primary cause of SMA by increasing levels of SMN protein, it is not a cure so additional, complementary therapies are still needed.
SMA causes motor neuron loss early on in life, so it is important to find ways to protect the remaining motor neurones. This study has identified a potential protective pathway, which can be targeted with a drug that is FDA-approved for another health condition. This is encouraging news, though further research is needed before the drug could be used in people with SMA.
Professor Gillingwater said:
“We are very excited by these encouraging results and hope that our work will help contribute to the ongoing efforts to find successful and effective treatments for SMA and related conditions. We are very grateful to The SMA Trust and Muscular Dystrophy UK for supporting this research.”
The study was published in the scientific journal, PLoS Genetics.