Researchers discover common cause of all forms of MND

American researchers have uncovered what could be a pivotal disease mechanism in all forms of motor neurone disease (MND).
The team, led by Prof Teepu Siddique at Northwestern University Feinberg School of Medicine in Chicago, describes in the prestigious journal Nature how problems with the ‘rubbish recycling’ system in motor neurones appear to be integral to the degeneration seen in MND.
Prof Siddique’s team initially discovered that mutations (mistakes) in a gene called UBQLN2 were the direct cause of the rare, inherited form of MND in a small number of affected families. UBQLN2 contains the instructions for making a protein called ubiquilin 2, which is part of a team that helps to recycle unwanted or faulty proteins in cells.
When the researchers went on to examine post-mortem samples of spinal cord and brain tissue from people with sporadic (non-inherited) MND and other types of the inherited form of the disease not caused by UBQLN2 mutations, in every single case they found ubiquilin 2 caught up in the tangled protein ‘clumps’ that are the hallmark of diseased neurones. This indicates that even when the UBQLN2 gene is not faulty, ubiquilin 2 still contributes to the disease process.
Although this finding comes hot on the heels of other important breakthroughs in recent years, this is the first time that scientists have seen evidence of a dysfunctional process common to all types of the disease, suggesting that it could provide an important target for future drug development. These results will now need to be verified by other research teams.
Dr Belinda Cupid, Head of Research Development at the Motor Neurone Disease Association, said: “This is a big news story for motor neurone disease research. The discovery of mutations in the UBQLN2 gene in families with the rare, inherited form of motor neurone disease has unlocked the significance of this damaged protein in all forms of the disease.
“We’ve known for some time that the waste and recycling system in motor neurones is damaged, but this is the first time that there has been direct proof. This discovery provides researchers with an exciting new avenue to explore as they search for an effective treatment.”
To go behind the scenes of this research breakthrough, read the latest from our research blog.

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