Edinburgh stem cell discovery gives insight into MND

26 February 2013

A discovery using stem cells from a patient with motor neurone disease (MND) could help research into treatments for the condition.

Profs Siddharthan Chandran and Ian WilmutThe study used a patient's skin cells to create motor neurons - nerve cells that control muscle activity - and the cells that support them, called astrocytes.

Researchers studied these two types of cells in the laboratory. They found that a protein expressed by abnormalities in a gene linked to motor neurone disease, which is called TDP-43, caused the astrocytes to die.

Although TDP-43 mutations are a rare cause of MND, scientists are especially interested in the gene because in the vast majority of MND patients, TDP-43 protein (made by the TDP-43 gene) forms pathological clumps inside motor neurons.

This study shows for the first time that abnormal TDP-43 protein causes death of astrocytes. The researchers, however, found that the damaged astrocytes were not directly toxic to motor neurons.

Better understanding the role of astrocytes could help to inform research into treatments for MND.

The study was led by Prof Siddharthan Chandran, Director of the Anne Rowling Clinic, and his team at the Edinburgh Euan MacDonald Centre for Motor Neurone Disease Research. It was carried out in collaboration with King's College, London, Columbia University in New York, the University of California and the Gladstone Institutes in San Francisco. The study was funded by the Motor Neurone Disease Association.

These findings, published in the journal Proceedings of the National Academy of Sciences, are significant as they show that different mechanisms are at work in different types of MND.

Serio A et al. Astrocyte pathology and the absence of non-cell autonomy in an induced pluripotent stem cell model of TDP-43 proteinopathy. PNAS 2013

Prof Chandran said: "Motor neurone disease is a devastating and ultimately fatal condition, for which there is no cure or effective treatment. It is not just a question of looking solely at motor neurons, but also the cells that surround them, to understand why motor neurons die. Our aim is to find ways to slow down progression of this devastating disease and ultimately develop a cure."

Dr Brian Dickie, the MND Association's Director of Research Development, said: "From a therapeutic perspective this finding is important because it means that specific treatments targeted at astrocytes may only be relevant and effective, in specific subsets of patients who will have to be carefully selected for drug trials."

Dr Steve Finkbeiner, Associate Director of Neurological Research at the Gladstone Institutes, said: "We were delighted to be part of this international team, which brought together critical tools, innovative technologies and complementary expertise to do something that no single group could. We are hopeful that the creation of human models of ALS will deepen our understanding of the disease in ways that will help us ultimately find relevant therapies for patients."

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