Changing fashions of MND models

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Models of MND are important both to understand the causes of MND and to quickly, efficiently and accurately screen and develop new treatments for it.

A number of key developments both in terms of technological know-how and new understanding of genetics of MND have led to the development of new models discussed at on the last day of the symposium.

Stem cells
The session was opened with a presentation on what is arguably the most glittering and exciting of these new models, that of using so called ‘iPS’ cells. The principle behind iPS cells (induced pluripotent stem cells to give them their full name), is that it’s possible to take a skin cell from someone with MND, coax it back into basic stem-cell-like state and then change it into motor neurones. The idea that this was even possible was scientific heresy say five years ago. The beauty of this technique is that you then have living human motor neurones in dish in the laboratory.

Dr Kevin Eggan from Harvard University Massachusetts USA is one of the leading lights in this technology and he treated us to an update of his latest research. “In itself, ALS is an interesting test tube for stem cell research” he said, adding “this is my first ALS meeting, I’ve enjoyed it and learnt a lot”. Aswell as being the first time that it was possible to study the cells directly affected in MND (motor neurones), iPS techniques also allow researchers to study the behaviour of motor neurones at as close to the actual disease conditions as possible.

Are they really motor neurones?
In the first part of this talk Dr Eggan explained and demonstrated that the cells that he and his colleagues have grown really are motor neurone-like and that they do behave like motor neurones. However he did caution that this model is not the panacea of ALS models, it’s an arrow in a quiver of techniques.

How do these motor neurones behave?
The second half of his talk concentrated on whether these human motor neurone models behave differently to motor neurones grown from skin cells of unaffected people.

When given the same growing conditions, motor neurones derived from people with SOD1 mistakes (mutations) were found to be less plentiful when growing ‘in a dish’ than those derived from healthy individuals. The SOD1 motor neurones also display a different pattern of electrical activity (transmitting electrical activity, is, after all, one of the main functions of motor neurones). The next steps of this research will be to double check that the effects seen in cells with SOD1 mutations really are due to this faulty gene and investigate the effects of other known genetic causes of MND in these cells.

Of mice and men
Moving from a new model to an old and arguably less fashionable one, Dr Greg Cox was given the title of “Are mice a good model for human ALS”. His first slide was to turn this question on its head and state that humans are a terrible model for mouse ALS! His point was that there are so many things that are unknown in human MND that generating a truly accurate mouse model for it was an almost impossible task. Saying this, he went on to discuss three key essentials for any mouse model, so called face, construct and predictive validity. Towards the end of his presentation he shared some results of one of this own studies, explaining that there is an area of our genetic code, not identified in MND before, that seems to carry a mistake that causes symptoms of MND.

Read our press release from day three of the symposium.

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