A new study has explored a mouse model of motor neuron disease (MND) that carries the most common genetic mutation linked to the condition, helping researchers understand how toxic proteins build up in the nervous system and whether future treatments might help stop them.
The mutation, found in a gene called C9orf72, is responsible for around 1 in 12 cases of MND. It involves a small section of DNA repeated hundreds or thousands of times. These mutations trigger the production of toxic proteins, which accumulate in neurons and are thought to play a key role in disease progression.
To study this, researchers used a harmless virus commonly used in genetic research that does not cause disease in mice to deliver the mutation into the brains of newborn mice. Some mice received a short, harmless version of the gene (as a control), while others received a mutated version. The team then monitored the mice, tracking their movement, memory, and behaviour and later analysing their brains and spinal cords.
They found that the mice with the mutation did produce the toxic protein poly-GP, just as expected. Treating the mice with an experimental therapy known as an antisense oligonucleotide (ASO) could reduce this to normal levels. ASOs are short synthetic molecules that can block or reduce the production of specific proteins.
One ASO, BIIB078, is already being tested in clinical trials for people with changes to C9orf72. It targets C9orf72 RNA, promoting its breakdown and reducing the production of toxic proteins associated with the disease. While early trial results have been mixed, the potential of ASO treatments in MND research is promising, and more research is needed to find a suitable treatment.
While the model successfully recreated this key disease feature, it didn’t show other typical signs of MND, such as neuron loss or changes to a protein called TDP-43. This suggests that although the model helps study some aspects of MND, it doesn’t fully replicate the complexity of the human disease. This highlights the limitations of individual models and underscores the importance of using multiple systems to study different aspects of the disease.
Despite the model’s limitations, the findings strongly support the ongoing development of ASO treatments. This reinforces the need to use multiple models to study different aspects of MND, providing reassurance and confidence in the direction of our research. This is why our researchers have created a national network of standardised lab models, making it easier to test new ideas and reproduce findings across multiple labs.
This research snapshot was created using the University of Sheffield’s Readable Research series, which helps turn technical science into clear, meaningful updates. A lay summary of the above research paper can be found here.
To stay informed about the latest MND research and contribute to the ongoing efforts, follow the UK MND Research Institute on social media or sign up for our newsletter.
