Investigating how C9orf72 MND potentially causes nerve cells to no longer respond to oxygen deprivation and how this might lead to MND.
PhD Student: Ergita Balli
Principal Investigator: Dr Ryan West
Lead Institution: University of Sheffield
MND Association Funding: £114,907
Funding dates: October 2023 - March 2027
About the project
A mutation in a gene called C9orf72 is the most common genetic cause of MND. This mutation results in the build-up of 5 toxic proteins, called dipeptide-repeats (DPRs), in the nervous system of people living with MND. However, how DPRs cause motor neurone death remains unclear. Previous evidence suggests one these DPRs, often considered to be the most toxic, impairs the ability of nerve cells to respond to reduced levels of oxygen (hypoxia). These low oxygen levels are known to occur during MND because of a weakened respiratory system, however it may also occur before people show symptoms. This can be due to environmental stresses such as intense exercise, sleep apnea or smoke inhalation, which have all been observed as MND risk factors. This project aims to investigate how DPRs cause nerve cells to no longer respond to oxygen deprivation and how this may lead to MND.
What could this mean for MND research?
This project looks to understand more about C9orf72-related MND and how the mutation may lead to a certain process to go wrong within the body. Once researchers have understood how the mutation causes this process to go wrong, they can then start to see if it can be prevented or corrected. This could potentially help to stop MND from developing or help to slow the progression of the disease.
Project code: 909-792
