Exploring and attempting to correct metabolic changes in models of C9-MND.
Principal Investigator: Dr Scott Allen
Lead Institution: University of Sheffield
MND Association Funding: £314,989
Funding dates: November 2025 - October 2028
About the project
MND affects not only the motor neurons, but also other cells in the brain and spinal cord that play important roles in supporting motor neurons. One of these cell types, called astrocytes, provide energy to motor neurons in the form of metabolites, which are the breakdown products from food. In C9orf72 MND, the most common form of genetic MND, astrocytes are not able to produce energy efficiently and this makes them less supportive towards motor neurons. In particular, the way that astrocytes process an important metabolic molecule called pyruvate, which helps to fuel the cell, is changed.
In this project, the researchers will explore how the C9orf72 gene causes this change and attempt to correct it. To do this, they will use cells from people with MND and fly models of C9-MND to assess how the processing of pyruvate is changed in response to natural ageing and cellular stress conditions. The researchers will then compare their data with metabolic analyses of cerebrospinal fluid and blood samples from people with MND, to see how the changes in the models of MND match the changes seen in the body fluids of people with MND.
What could this mean for MND research?
It is hoped that the project will help us to better understand the causes of metabolic changes in MND. Understanding these changes may provide an opportunity to identify new therapeutic targets for MND, in order to correct energy production. Correcting energy production might help to improve the health and survival of motor neurons. The research might also show that metabolic changes can be used as a biomarker for MND. Biomarkers are measurable changes in the body that might be able to help to diagnose and monitor the progression of MND.
Project code: 2459-791
