Spinal muscular atrophy (SMA) is a rare, genetically inherited neuromuscular condition that causes progressive muscle weakness and loss of movement as a result of muscle wasting (atrophy). There are now three therapies that people with SMA can access in the UK: nusinersen (also known as Spinraza), risdiplam (also known as Evrysdi), and a gene therapy called Zolgensma.
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. The enlargement of these motor units is an important part of the disease process in people with SMA. Enlarged motor units are thought to experience more oxidative stress (an imbalance in oxygen-containing molecules, which causes harm to cells), which has a negative impact on their survival.
What are the aims of the project?
This project aims:
(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, and 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, and
(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.
Why is this research important?
This project may have an important impact on our understanding of SMA, and may help to improve treatment.