Harnessing the power of stem cells to unlock the secrets of MND

A groundbreaking stem cell research programme funded by the Association will enable scientists to perform detailed studies on human motor neurones containing known causes of MND.

The programme, led by Prof Siddharthan Chandran and Prof Sir Ian Wilmut (University of Edinburgh), Prof Chris Shaw (King’s College London) and Prof Tom Maniatis (Columbia University, New York), is the biggest research project the Association has funded and will build on two recent major scientific advances:

The researchers will generate iPS cells from the skin cells of healthy individuals and people with the rare, inherited form of MND that is directly caused by a fault (mutation) in the gene that produces TDP-43. Although TDP-43 gene mutations are rare, cells containing such mutations should offer insight into most forms of MND as the TDP-43 protein is thought to be important in most cases of the disease.

The iPS cells can then be induced to turn into either of the two main cell types known to be involved in the disease: the motor neurons which degenerate in MND; and other vital support cells called astrocytes, which are believed to play a fundamental role in the spread of the disease throughout the brain and spinal cord.

A human model of MND

This ability to grow human neural cells in the laboratory has been a holy grail for MND researchers for many years. A key aim of this particular programme will be to refine and optimise this procedure to generate as many cells as possible, ultimately creating a robust and well characterised model of human MND available to scientists across the world. This system could eventually allow the rapid testing of hundreds of thousands of drugs which may protect human motor neurons from degenerating, accelerating the drug discovery process.


'Mix and match'

Having generated iPS cells from healthy donors and those with a faulty TDP-43 gene, the programme’s researchers will be in a position to perform ‘mix and match’ experiments, growing motor neurones and astrocytes from different donors in the same dish (a process called ‘co-culture’). This will enable the researchers to examine how healthy and diseased neurones and astrocytes interact and, in particular, to see whether astrocytes containing faulty TDP-43 are damaging to motor neurones. This will provide insight into the role of both astrocytes and TDP-43 in the progression of MND and will address whether the disease spread seen in the human condition can be reproduced in the lab.


Homing in on pivotal pathways

During the final phase of the programme, samples from the ‘mix and match’ experiments will be examined for their ‘gene expression signatures’. This means showing which genes within the cells are being switched on and off at various times as the disease evolves. It is anticipated that when combined with similar studies being performed on post-mortem tissue and animal models of MND, researchers will be able to home in on the pivotal biochemical pathways that are altered in the disease, opening up promising new treatment strategies.


What does this research mean to me?

The programme will not investigate the use of stem cells themselves to directly treat MND. However, the programme will make valuable progress towards an effective treatment in two ways:

  • Through the development of a robust, cost-effective model for fast and efficient drug screening
  • By providing valuable insights into the key biochemical processes that underlie MND and could be targeted by new drugs.

Can I donate my skin cells for use in the programme?The researchers have already identified those people with TDP-43 mutations who will be donating their skin cells to the programme. They have also already obtained enough skin cells from healthy individuals.