Exploring mechanisms and therapeutic opportunities for abnormal TDP-43 functioning in C9orf72 MND.
Principal Investigator: Dr Jean-Marc Gallo
Lead Institution: King's College London
MND Association Funding: £338,404
Funding dates: October 2025 - September 2028
About the project
Changes in the C9orf72 gene, which is one of the most common genetic causes of MND, produces toxic proteins that are harmful to cells. However, targeted gene therapy approaches for the C9orf72 gene have not yet proved successful. Another key target for new therapies is the TDP-43 protein, which also forms toxic protein clumps in neurons in most cases of MND. However, the link between C9orf72 and TDP-43 remains unclear. In this study, the researchers are building on their previous work and using genetically engineered stem cell models to find new interactions between C9orf72 and TDP-43. They will explore the interactions between the proteins and also look at how these interactions affect the way that other genes are switched on and off.
What could this mean for MND research?
It is hoped that the information gained from this research will identify novel targets and interactions between key harmful proteins in MND. This will provide opportunity for the development of new treatments to target these, in the hope to slow and potentially halt the progression of MND.
Project code: 2487-791