Stem Cells To Unlock Secrets Of Motor Neurone Disease

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Main Category: Muscular Dystrophy / ALS
Also Included In: Neurology / Neuroscience;  Stem Cell Research
Article Date: 24 May 2010 - 9:00 PDT

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Being able to grow and program human motor neurones in the lab has been the dream motor neurone disease scientists for several years. The Motor Neurone Disease (MND) Association is funding its first ever stem cell research program with the aim of finding the secrets of this neurological condition.

Spelling - Motor Neurone Disease or Motor Neuron Disease are both possible spellings.

The program pulls together the expertise from four world-class leading researchers:

• Prof Siddharthan Chandran, the University of Edinburgh
• Prof Sir Ian, the University of Edinburgh
• Prof Christopher Shaw, King's College London
• Prof Tom Maniatis, Columbia University New York

The MND Association's innovative program will enable scientists, to perform detailed studies on human motor neurones containing known causes of MND.

Thanks to recent advances in stem cell research, it is now feasible to generate human motor neurones from donor skin cells in order to study the processes at work in health and disease.

Dr Brian Dickie, Director of Research Development, MND Association, said:

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, opening up promising new treatment strategies.

Prof Colin Blakemore, president of the MND Association, explained:

"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 MND Association has funded ground-breaking research defining the genes responsible for inherited forms of the disease. This is the next step towards the Association's goal of a world without MND.

The Research

The main objective of the Association's £800,000 ($1,200,000) 3-year program is to develop and characterize human brain cells, originated from the skin cells of MND patients with the hereditary TDP-43 form of the disease, as well as from 'control' donors who do not have MND and carry the normal TDP-43 gene.

Experts believe the TDP-43 gene is probably a direct cause of MND in around 1% of cases. However, the protein produced by that gene is found in up to 90% of MND cases. This discovery has been described as 'a seismic shift' in understanding the disease, as it points to TDP-43 having a key function in numerous forms of MND. The TDP-43 protein has also been linked to other conditions - especially some types of dementia - so it may prove to play a contributory role in a greater number of neurodegenerative conditions.

Initially, skin cells are 'reprogrammed' to generate induced pluripotent stem cells (iPS cells), which are very similar to embryonic stem cells. 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 neurones which degenerate in MND; and other vital support cells called astrocytes.

In MND, the motor neurons die - however, we also know that the disease is not just restricted to these cells. The support cells that normally play a role in nurturing motor neurones can unintentionally cause damage, and it is through this mechanism that scientists believe that the disease spreads further in the central nervous system - from one part of the brain and spine to the next.

The MND Association's program will focus on a fundamental question of whether the support cells from healthy or TDP-43 mutant gene carrying patients are harmful or beneficial to motor neurones. In addition, experiments growing motor neurones 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 lab.

The researchers

Prof Siddharthan Chandran, Euan MacDonald Centre for MND Research at the University of Edinburgh; Prof Sir Ian Wilmut at the Medial Research Council Centre for Regenerative Medicine at the University of Edinburgh; Prof Christopher Shaw at the Institute of Psychiatry, King's College London; and Prof Tom Maniatis of Columbia University New York will all be working on various components of this three stage programme.

Prof Siddharthan Chandran, the programme's principal investigator, will be working with Prof Sir Ian Wilmut to refine and optimise the reprogramming procedure to ensure as many healthy cells as possible can be generated.

Prof Chandran said:

Bringing together the genetic revolution of the last decade with the spectacular progress in stem cell research means we can now model human disease in a dish.

Prof Sir Ian Wilmut added:

This funding from the MND Association will help us to understand why specific nerves die in MND. This is a critical next step towards the ultimate goal of developing an effective treatment.

The studies to examine the general health and structure of the different cell types when interacting with each other will be carried out at the University of Edinburgh and also by leading MND researcher Prof Christopher Shaw. Prof Tom Maniatis will work on the third stage of the programme by identifying 'gene expression signatures' associated with the disease.

Dr Brian Dickie 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 neurone disease research and enhancing future international research collaboration. Only by working together across the globe will we achieve our goal of truly defeating MND.

Motor neuron disease is a serious and incurable form of progressive neurodegeneration - over time the nerves in the spine and brain progressively lose function. In the case of motor neuron disease, motor neurons - types of nerve cells - are affected.

The renowned English physicist, Stephen Hawking, and guitar virtuoso Jason Becker are living with motor neuron disease.

There are different forms of motor neuron disease

• ALS (amyotrophic lateral sclerosis) is the most common form and accounts for approximately 60% to 70% of all cases.
• PBP (progressive bulbar palsy) accounts for about 20% of all cases.
• PMA (progressive muscular atrophy) accounts for the remaining 10% of cases.

In all three MND forms symptoms are very similar. However, they progress at different speeds.

PLS (primary lateral sclerosis) is a very rare form of MND. PLS, unlike the other forms, is not fatal. In some very rare cases, patients with PLS eventually have ALS.

Written by Christian Nordqvist
Copyright: Medical News Today
Not to be reproduced without permission of Medical News Today

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