New genetic cause of MND suggests cellular ‘traffic jams’ may play a role in all forms of MND

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As the afternoon was drawing to a close in the office yesterday, we learnt of an exciting new MND research paper that had been published in the prestigious journal, Nature. The research suggests that a rare mistake (mutation) in gene called ‘Optineurin’ (OPTN) can cause MND and they also suggest that OPTN may be involved in causing the disease in all forms of MND.

After reading the abstract, which provides a brief overview of what the researchers found, we wanted to know more. However, the way that some journal articles are accessed –including this one, is a bit like a locked novel. You can freely read the blurb of the book (the abstract) but to get the nitty-gritty details involves either asking the author for a copy, or by paying £30 for access. We decided to email the researchers as our first port-of-call to ask them if we could borrow a copy. As the researchers are based in Japan and are many hours ahead of us, we then had to wait patiently until this morning to find out whether in their working day they had obliged. Luckily for us, the researchers were extremely generous and speedily provided us with the paper for free so that we could explain what they did and what they found to all of you!

Overall, the researchers studied the genetic spelling differences of 16 people from close blood relative marriages – so called ‘consanguineous marriages’, 76 people with the inherited form of MND, and 597 people with the randomly occurring sporadic form of the disease.

From this they identified eight people with mutations in OPTN, seven from close blood marriages and one from a sporadic case. To make sure that the gene mistakes were not a ‘common’ spelling error that happens by chance, they also checked their results against controls who did not have the disease. They could not find the spelling difference in any controls and  it is likely to be the cause of the disease for these people.

However, if we dig a little deeper into this research, the story is not just about identifying a new genetic cause of the disease for some families. It was more about finding out what goes wrong on a cellular level which may give us more clues about what causes the disease for all types of MND.

By studying what goes wrong on a cellular level, the researchers were able to find out that MND may be triggered by a loss of function of OPTN, where it plays an important role in the trafficking of substances around the cell and indeed out of the cell. It also plays an important role in regulating cell death.

Further to this, the researchers also found that OPTN is faulty in both cells that are affected by SOD1 mistakes as well as TDP-43 mistakes (two previously identified genetic causes of MND). As the product of these gene mistakes are usually never found together, OPTN may be a more general ‘marker’ for all types of MND.

This is exciting research and we look forward to seeing more research into OPTN in the near future. To find out more information on this research finding, keep an eye out for a new ‘news in research’ article on our website. Or, you can read the scientific abstract on the Nature website.

As you may already be aware, identifying the causes of MND is one of our research priorities as set out by our research strategy. We are funding a number of projects – including a major international research collaboration that is hunting for genes, to learn more about the causes MND.

To let us know your thoughts on this research finding, please leave us a comment below by clicking on the orange ‘leave a comment’ button below the post.