Last year, we introduced a PhD Studentship that we are funding at the University of St Andrews. Under the supervision of Dr Gareth Miles and Prof Siddharthan Chandran, the student working on this project, Amit Chouhan, is investigating why electrical signalling goes wrong in MND.
As the project enters its second year, Amit and the team have made some important discoveries…
Why is faulty electrical signalling a problem in MND?
Motor neurones work by sending electrical signals from the brain and spinal cord to the muscles, which instruct them to move. In MND these signals become faulty, so the muscles can’t move and become weak.
To investigate why this occurs, Amit is studying electrical signalling in motor neurones that have been created from the skin cells of people with MND using stem cell (iPSC) technology.
Early tests suggest that there is an initial boost in electrical signalling, but over time it decreases and becomes faulty. Understanding why this happens will help us to design new and effective therapies..
How are the electrical faults being investigated?
Amit is focusing on the ion channels in the motor neurones. Ion channels are essential for regulating where the electrical signals flow and how much flows.
If you think of the signals as water flowing through a canal, the ion channels are a bit like the locks at the canal – they open and close to allow the signals through. It is vital that the signals get through to the muscles in the right amounts. If there is a problem with the locks (ion channels), then the water (signals) might be too high or low, which means the muscles won’t work properly.
To analyse this, Amit grew iPSC motor neurones in a dish in the lab. He recorded the electrical signals flowing through the ion channels across a range of time points.
What did the tests find?
One of the electrical signals was significantly increased in the motor neurones of people with MND compared to those without, at later time points. There were also changes in one particular ion channel. These results support that electrical signalling is faulty in MND.
Next steps: involvement of the glial cells
The team recently discovered that glial cells are important for electrical signalling. Glial cells are the support cells of the nervous system – they carry out a range of jobs that help the motor neurones to function well, for example, providing structural support and nutrients. Their findings highlight that these glial cells play a much bigger role in electrical signalling than previously thought, providing us with new knowledge that will help to design future research.
Amit is now growing a new set of motor neurones and glial cells together in the lab. He will conduct new tests and compare his results to the findings from year one. This will help to confirm which signals and ion channels are affected in MND, and reveal new targets that will help in the development of much needed treatments.