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Stem cell programme into Motor Neurone Disease

24 May 2010

Scientists at the Institute of Psychiatry (IoP), King's College London (KCL) are working on the first ever stem cell research programme into Motor Neurone Disease (MND). Recent advances in stem cell research mean it is now possible to generate human motor neurons from donor skin cells in order to study the processes at work in health and disease.

The project funded by The Motor Neurone Disease Association will bring together world-class expertise from four leading researchers:  Professor Christopher Shaw from the IoP, Professor Siddharthan Chandran and Professor Sir Ian Wilmut from the University of Edinburgh and Professor Tom Maniatis of Columbia University New York.

The ability to grow and programme human motor neurons in the laboratory has been a holy grail for MND researchers for many years.

Christopher Shaw, Professor of Neurology and Neurogenetics at the IoP, said: 'Pharmaceutical companies have drug libraries containing millions of potentially useful compounds and yet we can only test a handful of these in clinical trials every year. Our goal is to grow motor neurons from patient skin cells in order to identify which drugs can slow or reverse the disease process.  It will be a huge challenge, but if we are successful it will be a great step forward in advancing drug discovery.'

MND kills five people everyday in the UK. Life expectancy for those with MND is short - around two to five years and around half of those diagnosed with MND die within 14 months. This cruel condition leaves people trapped in a failing body unable to walk, talk or feed themselves. There is no cure and no effective treatment. The cause of the disease is only known in 5% of all cases. Therefore the need to unlock the secrets of this devastating disease and progress research is imperative.

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.

 The TDP-43 gene appears to be a direct cause of MND in around 1 per cent of cases but 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. (For further information on TDP-43 and its role in this programme please see the background briefing paper.)

The skin cells are initially ‘reprogrammed’ to generate induced pluripotent stem cells (iPS cells) which are very similar to stem cells derived from human embryos. 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.

Although it is the motor neurons that die in MND, it is known that the disease is not solely restricted to these cells. The support cells that normally play a role in nurturing motor neurons can inadvertently cause damage, and it is through this mechanism that scientists believe that the disease spreads from one part of the brain and spine to the next.

The research will address a fundamental question of whether the support cells from healthy or TDP-43 mutant gene carrying patients are injurious or protective to motor neurons. In addition, experiments growing motor neurons and support cells from different donors in the same dish (a process called ‘co-culture’) will address whether this disease spread seen in the human condition can be reproduced in the laboratory. 

Dr Brian Dickie, Director of Research Development at the Motor Neurone Disease Assoication concludes: '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 neuron disease research and enhancing future international research collaboration. Only by working together across the globe will we achieve our goal of truly defeating motor neuron disease.'

 

 

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