Nature, nurture, genetics and / or chance – what causes MND?

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Trying to understand what the different underlying factors are towards developing MND has always been a goal for ALS research.

MND Association funded researcher and clinician Professor Ammar Al-Chalabi from King’s College London, gave a talk on this topic at the opening session of the 23rd International Symposium on ALS/MND in Chicago. A record number of over 900 delegates gathered to hear his overview of where we are. It was a clear, informative, humorous talk with added technical wizardry!

“People say that this looks like Voldemort, but actually it’s me!” he commented on showing a whole head MRI. Prof Al-Chalabi used this picture to explain the differences between upper and lower motor neurones (upper motor neurones from the brain to the spinal cord and lower motor neurones from the spinal cord to the muscles).

MND is an ‘umbrella’ term for a number of related clinical diagnoses, including ALS, PMA and PLS – the distinctions are made by whether upper or lower motor neurones are affected. However, if you feed lots of data about people with all types of MND into a computer, it comes up with a different group of categories of MND – so there must be more to the causes of this disease than meets the eye. So going back to the title of his presentation are they nature, nurture, genetics or chance?

To look at these questions as a whole Prof Al-Chalabi used an analogy of the great fire of London. The first thing that he commented on was that some buildings were vulnerable to the fire (wooden ones) and some weren’t (those made of stone, with walls around them). The chance element was that the fire start in the east and spread west – due to a gale that day – the direction of the wind is generally in the other direction.

In MND, the chance finding is the hardest to investigate – if we can’t explain it, we’ll explain it by chance! The next section of his talk he gave an overview of some of the many factors that researchers have investigated into looking at the ‘nurture’ aspects of developing MND (a field of research known as epidemiology). Looking at the age that people develop MND, whether there are ‘hotspots’ of areas where people are more likely to develop the disease, links between physical activity and smoking; he said that it was hard to draw conclusions, saying that smoking might be a ‘pre-risk’ factor and the link between MND and physical activity is still being investigated.

The last part of the talk was looking at the genetic component as to why people might develop MND, giving an overview of the latest disease-causing (or primary gene mutations) and risk factor genes that have been found to date. Using illustrations of real-time animations from the Howard Hughes Medical Institute Prof Al-Chalabi described some of the broad categories the gene defects fall into: RNA processing, protein re-cycling system (the proteasome) and those linked to the internal skeleton on the cell (the cytoskeleton).

Perhaps not suprizingly, he concluded that of nature, nurture or genetics as the cause of MND “overall, all these factors play a part, it’s impossible to separate them”.

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