Scientists find second MND gene
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26 Feb 2009
 A collaborative research project involving Christopher Shaw, Professor of Neurology and Neurogenetics, Institute of Psychiatry has revealed that mutations in a gene called FUS (fused in sarcoma) cause familial Motor Neuron Disease (MND). This is the second gene to be discovered for MND in just one year and is an important step towards understanding disease mechanisms.
The research is published online in two back-to-back papers in the US journal Science this week. Other collaborators on this study included Dr Tom Kwiatkowski at Massachusetts General Hospital (MGH) and Professor Robert H Brown at University of Massachusetts, USA.
Professor Christopher Shaw, Head of Department of Clinical Neurosciences and Director of the King's Clinical Neurosciences Institute and senior author of the paper explains: 'The new gene, called FUS, is a very important clue as to what causes motor neurons to degenerate. It links in with TDP-43, which is deposited in motor neurons in 90 percent of all people with MND.
'The genetic pieces of the jigsaw puzzle are beginning to fit together leading us in new and exciting directions of research. There are also major implications for diagnosis and treatment.
'We are very excited about this latest discovery and the collaboration between the Boston and London research groups has been crucial in this breakthrough. It is only by understanding the fundamental disease mechanisms that we will find a cure.'
These findings will not only help doctors to counsel those families at risk of MND but crucially aid researchers to develop better models of disease. The gene FUS is shown to be related to the TDP-43 gene found by Professor Shaw’s team last year. Thanks to this development scientists now have two more genes with which to map out the origins of this dreadful disease and develop drugs to combat it.
Research progress
For nearly a decade, researchers at King's and MGH have been hunting a gene that they knew must lie on the 16th chromosome. Following up on a lead from Dr Kwiatkowski and Professor Brown at MGH, Professor Shaw’s team identified a FUS mutation in their chromosome 16 linked family and subsequently found that 4 percent of all families had FUS mutations. These were only detected in those with the inherited form of MND, which accounts for 10 percent of all cases.
This is the fourth MND-causing gene to be identified after 20 years of genetic research. The first gene, called SOD1, was discovered in 1993, the second ANG is a growth factor for nerve cells discovered in 2006. The new protein FUS has a very similar role to the third gene TDP-43, mutations in which were first described by Professor Shaw’s group in 2008.
This latest discovery has been made possible by the longstanding collaboration between researchers and co-funding by research organisations, including the ALS Association in the US and the MND Association in the UK.
Commenting on this latest discovery, Dr Belinda Cupid, Research Manager at the MND Association said: 'This is the second MND-causing gene to be identified in less than 12 months, a reflection of the accelerating pace of research around the world.
'Not only will it open up an entirely new avenue of scientific investigation, it will also allow researchers to compare the different known causes of MND and start to home in on the main biochemical events that cause motor neurones to die. This understanding will lead to new approaches to defeat this cruel disease.'
The FUS protein, made by the FUS gene, normally carries out multiple functions within motor neurones. These include regulating how gene messages are created, modified, and transported in order to make proteins which are the building blocks of all cells.
The mutations were identified by detailed gene sequencing in families with an inherited form of the disease linked to chromosone 16. Usually the FUS protein works in the cell’s nucleus, but the mutation causes the protein to be abnormally located in the cell, outside the nucleus and it forms large aggregates within motor neurons in people carrying the mutations. More work is now needed to determine how the FUS and TDP-43 cause MND.
MND is the name given to a group of related diseases affecting people in different ways. ALS is a progressive neurodegenerative disease that affects nerve cells in the brain and the spinal cord and is the most common form of MND. There is currently no cure for this condition and around 5,000 people in the UK at any one time are affected. Life expectancy for most people with MND is two to five years, and around half will die within 14 months of diagnosis. Up to 10 percent of cases of MND are the inherited and known as familial MND.
[Image credit - Dr Tibor Hortobagyi, Senior Lecturer and Consulant Neuropathologist, MRC Centre for Neurodegeneration Research, Institute of Psychiatry, King's College London - A large inclusion is detected by anit-FUS antibodies within the cytoplasm of an anterior horn motor neuron in a patient who carried the R521H FUS mutation. The adjacent motor neurons reveal normal nuclear staining and no inclusion. Immunopositive neuronal processes are also noted.]
King’s College London
King’s College London is one of the top 25 universities in the world (Times Higher Education 2008) and the fourth oldest in England. A research-led university based in the heart of London, King’s has 19,700 students from more than 150 countries, and 5,400 employees. An investment of over £500 million has been made in the redevelopment of its estate in recent years
King’s has an outstanding reputation for providing world-class teaching and cutting-edge research. In the 2008 Research Assessment Exercise for British universities, 23 departments were ranked in the top quartile of British universities; over half of our academic staff work in departments that are in the top 10 per cent in the UK in their field and can thus be classed as world leading. The College is in the top group of UK universities for research earnings and has an overall annual income of approximately £450 million.
King’s has a particularly distinguished reputation in the humanities, law, the sciences (including a wide range of health areas such as psychiatry, medicine and dentistry) and social sciences including international affairs. It has played a major role in many of the advances that have shaped modern life, such as the discovery of the structure of DNA and research that led to the development of radio, television, mobile phones and radar. It is the largest centre for the education of healthcare professionals in Europe; no university has more Medical Research Council Centres.
King's College London and Guy's and St Thomas', King's College Hospital and South London and Maudsley NHS Foundation Trusts are working together to create King’s Health Partners - a world-leading Academic Health Sciences Centre (AHSC). King’s Health Partners brings together an unrivalled range and depth of clinical and research expertise, spanning both physical and mental health. Our combined strengths will drive improvements in care for patients, allowing them to benefit from breakthroughs in medical science and receive leading edge treatment at the earliest possible opportunity. For more information, visit http://www.londonsahsc.org
Further information
Camilla Palmer, Public Relations Manager
Institute of Psychiatry, King's College London
Email: camilla.palmer@iop.kcl.ac.uk Tel: 020 7848 0483
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Published on 03/04/2009 16:00:00
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