New gene variation which causes MND discovered in novel biological pathway

Scientists have discovered a new gene variation that causes motor neurone disease (MND) in a novel biological pathway that until now hasn’t been linked with neurodegeneration.
The findings for the pioneering study, conducted by a team of researchers from the Sheffield Institute for Translational Neuroscience (SITraN) and the NIHR Sheffield Biomedical Research Centre (BRC), could potentially help to identify completely new ways of treating MND which currently affects over 5,000 people in the UK.
MND, also known as Amyotrophic Lateral Sclerosis (ALS), is a devastating neurodegenerative disorder that affects the nerves – motor neurones – that form the connection between the brain and the muscles. The messages from these nerves gradually stop reaching the muscles, causing them to weaken, stiffen and eventually waste. The progressive disease affects a person’s ability to walk, talk, eat and breathe. Approximately 10 per cent of MND cases are inherited but the remaining 90 per cent are caused by complex genetic and environmental interactions which are not well understood – this is known as sporadic MND. There is currently no curative therapy.

Dr Johnathan Cooper-Knock, NIHR Clinical Lecturer at the University of Sheffield’s Institute for Translational Neuroscience (SITraN), explained the impact of the ground-breaking research which is helping scientists to understand the fundamental genetic basis of MND.
“This new gene does not fit into a biological function that we already know is associated with MND,” said Dr Cooper-Knock.
“That means that this finding has potential to identify completely new ways of treating MND.
“The mutations found in patients were shown to be toxic to neurons and, when expressed in zebrafish they produced muscle weakness consistent with MND. This work strongly suggests that the mutations are the cause of MND in the patients where they were identified.”
During the study, researchers genetically sequenced tissue from two related patients with an unknown familial form of MND and found a mutation in the substrate binding region of a glycosyltransferase enzyme called GLT8D1. They went on to screen a larger sample of 103 patients, five of whom had this mutation. The study revealed a new genetic subtype of MND.

University of Sheffield

" "