Readable Research is proud to be working with LifeArc who are making life science life changing. LifeArc is a not-for-profit medical research organisation which is leading the way for change in rare diseases and supports promising initiatives in global health. They help ensure great science achieves its potential and reaches patients faster.
One of their latest studies is about motor neurone disease (known globally as amyotrophic lateral sclerosis) and how, in order to properly research the impact of treatments being developed, scientists need to know the motor neurones produced from stem cells reflect how they behave in the real world, in those living with the condition or those who may go on to develop it.
This is vital to ensure the hugely important work of scientists in labs can be replicated in humans and it’s why researchers at LifeArc have examined the relationship, the differences and how to ensure consistency.
Kate Matheson, one of our Readable Research authors, has studied the research and produced a lay summary which has also been reviewed by Dr Scott Allen and an MND lay panel.
Background
Amyotrophic lateral sclerosis, more commonly known in the UK as motor neurone disease (MND) is a disorder that causes death of motor neurones, the cells that control our muscles. There is currently no cure for MND meaning those with the disorder often die a few years after being diagnosed.
To investigate how MND develops and potential ways to treat it, scientists replicate MND in the lab. One way of doing this is by taking cells from people, such as skin or blood cells, and placing them in a specific mixture of chemicals that cause them to change into stem cells. These stem cells are no longer able to perform their original job, such as being a skin or blood cell, but can now be placed in other, different chemicals to become whichever cells scientists wish to study, such as motor neurones.
Research has shown that many factors determine whether someone develops MND, including their genes. Genes are sections of DNA which are made into proteins that determine a person’s characteristics, for example, their hair colour or whether they have certain diseases, although not all diseases are genetic. Therefore, using stem cells taken from MND patients is useful for MND research as these cells have MND genes.
Why is the study important?
Currently, the motor neurones that are produced from stem cells can differ from each other from day to day and from batch to batch, and do not always mimic real motor neurones. This is partly due to unintentional changes in the conditions that the stem cells are exposed to. This affects MND drug discovery as results from experiments may differ each time they are carried out.
Scientists wish to identify the cause of these differences so that they can be fixed to ensure that the motor neurones are consistent with each other each time they are produced. One way researchers have attempted to make the motor neurons more consistent is by giving the stem cells specific small-sized molecules that control the way proteins within the cells talk to one another.
This study used this technique to see whether there were any differences between the motor neurones produced (from stem cells) and, for any differences found, what the cause of these were.
What did the authors do and how did they do it?
These small molecules were added to stem cells taken from eight MND patients, causing them to transform into motor neurones. Researchers completed this procedure fifteen times with different groups of stem cells to see if there were any differences in the motor neurones produced on separate occasions or by separate researchers. It took around three weeks for the stem cells to fully transform, at this point they were placed in labelling dyes that helped to visualise the motor neurones as well as identify certain proteins that should be present if the stem cells had transformed properly into neurones.
Photographs of the dyed motor neurones were then taken through a microscope so that the researchers could observe how well they transformed and if they were consistent with each other. For example, they examined the motor neurones shape, stage of development and whether there was any clumping together. Additionally, stem cells taken from the same patients had their genes tested for any irregularities that may have impacted on how well the stem cells transformed into motor neurones.
What are the results?
Upon examining the motor neurones, researchers found that there were a lot of differences between them. For example, over half of the motor neurones differed from one another in the size of their neurites, which are long structures on neurones used to speak to one another. It was identified that the specific occasion the procedure was performed (from the fifteen carried out) was most responsible for causing these differences, followed by which researcher performed the procedure. The origin of the stem cell (from the eight patients) was only responsible for a small amount of the differences observed in the motor neurons.
Furthermore, researchers discovered that the stem cells with no genetic irregularities produced motor neurons containing the appropriate proteins, suggesting that they had developed successfully. These motor neurons also had fewer differences between them than those with genetic irregularities. On the other hand, the motor neurons that lacked genes were more clumped together, were not shaped like typical motor neurons and also lacked specific proteins that would suggest they developed properly.
What do the findings mean going forward for people with the disease?
This study used small-sized molecules to transform stem cells into motor neurones. It found that the differences between the motor neurones produced were mainly because of differences between the procedures and the researchers that performed the procedures, rather than which patient the stem cells were derived from. This is promising as stem cells taken from different patients will have different genes, which is difficult to change. To lower the impact of procedural and researcher differences, robots could be used to perform the procedure as they show less inconsistencies than humans do. Doing so would make this small molecule approach to changing stem cells into motor neurones beneficial for future research into MND drug discovery.
This study also showed that differences between motor neurons could be lowered if stem cells with genetic irregularities are removed. Therefore, future studies into MND should test for genetic irregularities before changing stem cells into motor neurons to make sure the results of experiments are more consistent between cells.
Download LifeArc’s in-depth summary of this research >>
Paper title
Examining iPSC derived motor neuron variability and genome stability monitoring as a solution
Authors
Finbar Gaffey, David McCoull, Egle Vaitone, Erin Hedges, Christopher Lovejoy, Zhi Yao, Paul D Wright, Richard J Mead, Will Stebbeds
Publication details including date of publication
Nature, 12th November 2025 – https://www.nature.com/articles/s41598-025-23378-0