Scientists have discovered a new gene varitation 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 team of researchers 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 neurogenerative 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 persons'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.
"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, published in the journal Cell Reports, 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.
\Mutated GLT8D1 exhibits in vitro cytotoxicity and induces motor deficits in zebrafish consistent with ALS. Relative toxicity of mutations in model systems mirrors clinical severity. In conclusion, researchers have linked ALS pathophysiology to inherited mutations that diminish the activity of a glycosyltransferase enzyme.
Mutation in glycosyltransferase implicated in ALS
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