Clue to cause of motor neurone disease revealed in new genetic study

Researchers discover a fifth genetic mutation associated with typical motor neurone disease <em>- News Release</em>

Imperial College London News Release

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Monday 5 April 2010

Researchers have discovered a fifth genetic mutation associated with typical motor neurone disease, or amyotrophic lateral sclerosis, that has a similar pathological effect to certain genetic mutations revealed in earlier studies. Ultimately, the researchers hope that understanding what is causing motor neurone disease (MND) will lead to new avenues for treatment.

MND is a progressive neurodegenerative disease that attacks the upper and lower motor neurones. Degeneration of the motor neurones leads to weakness and wasting of muscles, causing increasing loss of mobility in the limbs, and difficulties with speech, swallowing and breathing.

The new research, published today in the journal Proceedings of the National Academy of Sciences and led by researchers from Imperial College London, provides strong further genetic evidence that the disease is caused by proteins clumping together in motor neurones, which are the cells that help to control the movement of muscles.

The effect of proteins clumping together in this way, known as protein aggregation, is toxic and it ultimately kills motor neurones. Protein aggregation is believed to be involved in other neurodegenerative diseases such as Alzheimer's disease and Parkinson's disease. Previous studies have found a similar association between genetic mutations linked to protein aggregation and MND.

Professor Stephen Hawking is a well-known example of a person with motor neurone disease

The newly discovered mutation, known as R199W-DAO, has been found in a family with a genetic history of MND. R199W promotes toxic protein aggregation inside motor neurones. It also interferes with levels of D-serine, which modulates the transfer of information between neurones. D-serine accumulates in the spinal cord in people with the sporadic form of MND, suggesting that this plays a role in the disease.

Professor Jackie de Belleroche, the lead author of the study from the Department of Medicine at Imperial College London, said: "Motor Neurone Disease is a fatal condition for which there is currently no cure. Our finding is one valuable piece in the puzzle to show what’s happening with the disease. Unfortunately we’re a long way from finding a cure for MND, but it’s only through understanding how MND works that we'll be able to find new ways to treat it."

The researchers discovered the new mutation after looking at 20 members of a family with the genetically inherited form of MND, known as familial MND. Children of a parent with familial MND have a one in two risk of inheriting the disease.

In the study, all of the family members with motor neurone disease had the R199W mutation, whereas none of the individuals with parents unaffected by the disease carried it.

Dr Brian Dickie, director of research development at the Motor Neurone Disease Association, said: "Identifying definitive causes of motor neurone disease (MND), no matter how rare, is of vital importance. It will allow scientists to compare one form of MND with another, to more rapidly identify the common biochemical events that dictate whether a motor neurone lives or dies, no matter what the original cause of the disease is. It serves as a springboard for much greater understanding of MND – and it is through this understanding that effective treatments will be developed."

The researchers did not find the R199W mutation when they looked at a larger population of unrelated people. They looked at the genetic makeup of 1,002 individuals, 780 of whom had no history of motor neurone disease, 23 who had sporadic MND, and 199 who had familial MND, and found no incidences of the mutation.

However, even though this mutation is rare, they believe that its presence in only those family members with MND means it provides valuable further clues about what is causing the disease.

This research was carried out by scientists from Imperial College London, King's College London and the Institute of Psychiatry, London. It was funded by the Motor Neurone Disease Association, the Smith's Charity, the American ALS Association, the Haywood Foundation, the Garfield Weston Foundation, and Land Securities Group.

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For further information please contact:

Laura Gallagher
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Imperial College London
e-mail: l.gallagher@imperial.ac.uk
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Notes to editors:

1. About Motor Neurone Disease (MND)

*There is currently no cure for MND and no effective treatment.
* Life expectancy for patients is just two to five years and around half of those with MND die within 14 months of their diagnosis.
* There are around 5,000 people living with MND in the UK and five people a day die in the UK from MND.

For further information about motor neurone disease please go to www.mndassociation.org or contact Louise Coxon, communications manager at the Motor Neurone Disease Association on 01604 611 843 or 07760 765 142.

2. About Imperial College London

Consistently rated amongst the world's best universities, Imperial College London is a science-based institution with a reputation for excellence in teaching and research that attracts 14,000 students and 6,000 staff of the highest international quality. Innovative research at the College explores the interface between science, medicine, engineering and business, delivering practical solutions that improve quality of life and the environment - underpinned by a dynamic enterprise culture.

Since its foundation in 1907, Imperial's contributions to society have included the discovery of penicillin, the development of holography and the foundations of fibre optics. This commitment to the application of research for the benefit of all continues today, with current focuses including interdisciplinary collaborations to improve health in the UK and globally, tackle climate change and develop clean and sustainable sources of energy. Website: www.imperial.ac.uk