Stem cell research reveals differences in cells from people with MND

Euan MacDonald Centre researchers and their colleagues have published exciting new findings based on their research on stem cells.

Our researchers have found ways to turn cells from donated skin biopsies into motor neurons ‘in a dish’ in the laboratory in order to study them more closely.

In this study, the researchers found that motor neurons that came from people with a particular type of MND – those who carry a mutation in a gene called C9ORF72 – displayed different electrical properties from those that came from healthy volunteers.

The different properties meant that these motor neurons were more likely to die under conditions that put the cell under chemical stress. Other neuron types were unaffected.

Doctors have long wondered why it is particularly the motor neurons that are affected in MND, while other neuron types remain healthy. These latest findings may help start to explain the difference.

When scientists make a discovery such as this, they need to confirm it by conducting a different type of experiment. In this case, the researchers looked for the same difference in brain cells that were donated post-mortem. Excitingly, they found the same difference in motor neurons from people with MND.

The work was led by Euan MacDonald Centre Director Professor Siddharthan Chandran, and involved Centre Investigators in Edinburgh (David Wyllie, Giles Hardingham, Colin Smith, Tim Aitman) and St Andrews (Gareth Miles).

The work also involved collaboration with researchers at King’s College London, Biogen (Cambridge MA) and inStem (Bangalore India) – with a total of 32 scientists credited in the publication. This illustrates well the global and collaborative nature of MND research.

Of course, studying a difference in one molecule in cells grown in the lab is very different from understanding MND in people. However by taking incremental steps such as this, scientists are able to build up an ever-more-detailed picture of what causes MND and thus, how to slow, stop and eventually reverse it.

Related links

Read the scientific publication: C9ORF72 repeat expansion causes vulnerability of motor neurons to Ca2+-permeable AMPA receptor-mediated excitotoxicity. Nature Communications, volume 9, Article number: 347 (2018) doi:10.1038/s41467-017-02729-0

Professor Siddharthan Chandran’s profile