Using stem cells in research
It is extremely difficult to obtain human motor neurones for study or to grow motor neurones from animal models of MND. Scientists are now learning how to encourage stem cells to develop into living motor neurones in the laboratory, providing a unique resource for MND research.
Researchers would like to use human motor neurones generated from stem cells to help them understand what goes wrong in MND.
Re-programming adult cells (iPS cells)
It is now possible to 'turn back the clock' on adult human skin cells, reprogramming them to turn back into embryonic-like stem cells that have the potential to generate neurones.
As these stem cells are created without the use of embryos, the technique avoids the ethical issues surrounding stem cell research. These cells are called 'induced pluripotent stem cells' or iPS cells.
How can iPS cells be used in MND research?
Researchers can re-programme skin cells from people with the inherited form of MND and turn them into motor neurones and supporting cells.
Because these neurones contain a genetic cause of MND, they will display characteristics of the disease. They could be used to understand the underlying mechanisms of MND and as a screen for selecting drugs that may be beneficial.
Our stem cell research
Below are some of the projects that use iPS cells, funded by the MND Association.
Studying the role of TDP-43 mutations in the transport of RNA
Dr Martina Hallegger (University College London) was awarded a Non-Clinical Fellowship by the Association in January 2016.
Abnormal deposits of the TDP-43 protein are found in the majority of cases of MND, and cause damage to the motor neurones. There is a part of the TDP-43 protein heavily linked to the development of TDP-43 deposits, this is called the low-complexity (LC) domain.
Dr Hallegger will look at how mutations in the LC domain are linked to MND. She will do this by studying motor neurones generated from iPSCs. Understanding the ‘knock on’ effects of LC domain mutations and how these might lead to protein deposits could enable the development of more targeted drugs.
Our reference: 959-799
Using iPSCs to understand the interplay between C9ORF72 and TDP-43
In previous research, Prof Kevin Talbot and Dr Ruxandra Mutihac (both University of Oxford) have begun to understand more about how the C9orf72 gene defect causes human motor neurones to die. These studies were conducted using nerve cells created from patient’s skin cells using iPS cell technology.
In this research project they are looking at the electrical activity of the nerve cells, how the nerves connect to muscle and how different parts of the cell contribute to the cells dying. They are using motor neurones from people with two different forms of inherited MND (those with C9orf72 and TDP-43 mutations respectively) to see any differences and similarities between them.
Our reference: 832-791
Using DNA Bank samples to create iPSC models of MND
Prof Chris Shaw, Prof Jack Price (both King’s College London) and Prof Siddharthan Chandran (University of Edinburgh) are carrying out a project using the already collected white blood cell samples within the UK MND DNA Bank. From these they will create a large number of new iPS cell models of MND. Ultimately creating an MND iPS cell bank, these models will enable researchers to better understand the disease and screen potential new drugs.
You can read more about their work on our research blog.
Our reference: 80-970-797