The opening presentation of this morning’s session of the International Symposium on ALS/MND set the tone for the rest of the day – almost literally, it was as if there was a neon light outside the lecture theatre saying ‘exciting science being presented here’.
Stem cells to study electrical activity of neurones
First up was Dr Kevin Eggan, he started his story by explaining that patients with motor neurone disease have more electrically active (more excitable) neurones than people who are healthy. This can be shown using things like transcranial magnetic stimulation. He wanted to investigate why motor neurones are more excitable, and he used induced pluripotent stem cells from two patients with a specific type of the SOD1 inherited form of MND to do this (find out more about induced pluripotent stem cells and the rare, inherited forms of MND on our website). Successfully creating functioning motor neurones from iPS cells is not any easy technique to master, and on his whistle-stop tour of elegant techniques, the first stop was to explain his ‘recipe’ for creating motor neurones. (iPS cell methods are a bit like a good cake recipe – it needs to produce the same results – or as near as they can – every time).
When measuring the electrical activity of motor neurones from iPS cells, he found the same thing that he saw in people – that the SOD1-MND motor neurones have more activity compared to activity in health motor neurones. Dr Eggan went to some length to show that this increased electrical activity was definitely due to the presence of the damaged (mutated) SOD1 gene – he engineered the iPS cells to remove the mutant SOD1 and replace it with an undamaged copy. He then gave the engineered motor neurones and the original SOD1 motor neurones to a colleague to who genetically analysed all of the cells blindly to confirm the engineering had worked – the colleague didn’t know anything about the presence of SOD1 and the engineering to remove it.
The next part of the study was to understand how or why mutant SOD1 changed the electrical activity of the cell. This was the most visually stunning part of his talk.
Flashing blue and red lights
Electrical activity in motor neurones (and other types of neurones) is caused by pores or ‘channels’ (tiny, tiny gaps) in the wall of the nerve cell opening to allow sodium into the nerve and sparking an electrical message. What stops your nerve cells constantly firing is the opening of another set of pores specific to potassium, causing potassium to move out of the nerve. (Thinking about this I’m reminded of those ‘In only’ and ‘Out only’ doors in restaurant kitchens).
Dr Eggan was using a new technique with an adapted pore that is sensitive to blue light – when blue light is shined on the motor neurones the channels open and they become electrically active, what’s more is that in his system the presence of electrical activity causes a tag on another part of the nerve cell to glow red. He showed some movies of the motor neurones from iPS cells in a dish in the presence of blue light – there were so many flashes of red light! It was like watching a mini thunder storm in a dish.. !! Dr Eggan’s work shows that the potassium brake on electrical activity doesn’t work so well in the SOD1 form of MND.
Getting up to speak after a visually spectacular talk wasn’t a task I would have wanted to do, but MND Association-funded Ruxandra Mutihac from Oxford University quietly and confidently added to the increasing ‘buzz’ in the room in her talk. Like Dr Eggan, Dr Mutihac was using iPS cells, this time from patients with the C9orf72-form of MND (see yesterday’s blog for more on C9orf72). She created these cells to understand more about why C9orf72 is toxic to motor neurones. Her studies showed that there changes in the role of calcium-controlled functions in motor neurones. The flashing neurones of Dr Eggan seemed quite gaudy in comparison to the beautiful laser microscopy images Dr Mutihac treated us to. I’d happily put one of these images on my wall in a frame!
Rest assured, the future of iPS to give us important insights into the causes of motor neurone damage and targets to treat it, is very bright indeed!
Would the fact that my son was, as a child, hyper active have any significance. He was a sporty athletic adult, worked hard and used his energy that way as an adult. His five year old son , one of twins, is also hyper active and I worry he may develop MND eventually.
While physical activity has been associated with MND (see our blog on physical activity and MND), the disease is likely to be caused by a combination of multiple factors and it is unlikely that one lifestyle factor would directly cause development of MND on its own.
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