The project brings together researchers Siddharthan Chandran and Ian Wilmut at Edinburgh University, Christopher Shaw of King’s College London and Tom Maniatis of Columbia University New York, with the aim of using induced pluripotent stems cells derived from people with the disease to generate human motor neurons with MND phenotypes.
The ability to grow and programme human motor neurones in the laboratory is a long-held objective of MND researchers. Brian Dickie, director of research development at the MND Association, says, “The technology is now available to allow us to build upon the recent, important discoveries made by researchers around the world. We have started to make real progress in understanding the causes of motor neurone disease and further investigation is needed to maximise the potential of stem cells to find effective treatments and we hope eventually a cure.”
“This international MND Association research programme will allow scientists to perform detailed studies on human motor neurones. As a result, we will be able to home in on the pivotal biochemical pathways that are altered in MND.”
Colin Blakemore, president of the MND Association, said, “Stem cells derived from patients offer the opportunity to create nerve cells in the lab in order to study the disease process in minute detail. There is great hope that this approach will enable us to unravel the mystery of MND – why and how particular nerve cells die.”
The principal aim of the £800,000 three-year programme is to develop and characterise human brain cells, derived from the skin cells of MND patients with the hereditary TDP-43 form of the disease and also from control donors who do not have MND and carry the normal TDP-43 gene.
While the TDP-43 gene appears to be a direct cause of MND in around 1 per cent of cases, the protein that the gene produces is found in up to 90 per cent of MND cases. This discovery has been described as ‘a seismic shift’ in understanding the disease, as it points to TDP-43 playing a pivotal role in many forms of MND. The TDP-43 protein has also been implicated in other conditions, in particular some forms of dementia, so it may prove to play a contributory role in a wider number of neurodegenerative diseases.
Dickie said, “This is a highly promising field of research to help increase our understanding of this disease. The outcomes from our programme will have a powerful impact in shaping the future of motor neurone disease research and enhancing future international research collaboration.”