Scientists gain insight into the cause and possible treatment of motor neurone disease
17 November 2008
BBSRC-funded researchers at UCL along with collaborators at King’s College London have identified a molecule that could be the key to understanding the cause of neurodegenerative diseases such as motor neurone disease (MND). This insight opens up the possibilities for developing new treatments to treat these devastating progressive conditions. The research is published today (17 November 2008) in the Proceedings of the National Academy of Sciences (PNAS) and is funded by BBSRC (Biotechnology and Biological Sciences Research Council) with the Medical Research Council and the Wellcome Trust.
Lead researcher Professor Patricia Salinas said: "For decades we have been studying how nerves communicate with their target muscles and we know that in diseases like MND the sites of contact between nerves and muscles become weak. However, many mysteries remain as to how these contacts form under normal circumstances and therefore it has been very difficult to see what has gone wrong in MND. The work we are publishing today puts another important piece of the puzzle in place and offers up a new possibility for developing drugs to treat MND and other neurodegenerative diseases."
Professor Salinas, with her husband Dr Simon Hughes – a researcher at King’s College London – has found that a signalling molecule called Wnt3 plays a crucial role in creating the connections, or synapses, between nerves and the muscles they control. It does this by assisting another molecule called Agrin, which coordinates construction of the synapse and organises the elements that make up the connection.
Professor Salinas continued: "Without properly formed synapses the muscle cannot receive the nerve signal that tells it to contract and hence we see the muscle weakness that is classic in MND. If we can build up a thorough picture to show how synapses are normally formed between nerves and muscles we can start to look for any elements that aren’t working properly in people with MND. This might also lead to strategies for nerve repair after an injury."
The team of researchers have looked at the function of Wnt signals in chickens, mice and in cells and in all three cases it was shown to enhance the effectiveness of Agrin.
Professor Salinas added: "Chickens that don’t have the Wnt signal in their developing wings have all of the muscle tissue that we would expect to see, but they don’t make strong connections between nerves and muscles. So we know that Wnt is definitely affecting synapse formation rather than anything else to do with muscles. Now that we understand the role Wnt plays we can begin to explore any role it plays in MND and whether it could be a good target for treating this type of neurodegenerative disease."
Professor Janet Allen, BBSRC Director of Research said: "We are delighted to see that work funded by BBSRC is making an impact on the understanding of serious conditions like MND. When scientists ask questions about normal biological processes they are often doing work that underpins better health and well being for people in the future."
Dr Belinda Cupid, Research Manager, MND Association, said: "We know from recent research that signs of motor neurone damage, on a cellular level, in models of MND occur very much earlier than the symptoms appear, so any new knowledge of how healthy motor neurones and muscles interact will give us new clues about what might be going wrong in those people affected by this cruel disease."
Notes to editors
This work is published in PNAS: "Wnt signalling promotes AChR aggregation at the neuromuscular synapse in collaboration with agrin", doi/10.1073/pnas.0806300105
The Biotechnology and Biological Sciences Research Council (BBSRC) is the UK funding agency for research in the life sciences. Sponsored by Government, BBSRC annually invests around £420M in a wide range of research that makes a significant contribution to the quality of life for UK citizens and supports a number of important industrial stakeholders including the agriculture, food, chemical, healthcare and pharmaceutical sectors. www.bbsrc.ac.uk
The Medical Research Council supports the best scientific research to improve human health. Its work ranges from molecular level science to public health medicine and has led to pioneering discoveries in our understanding of the human body and the diseases which affect us all. www.mrc.ac.uk
About King's College London
King's College London is one of the top 25 universities in the world (Times Higher 2007) 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. King's has an outstanding reputation for providing world-class teaching and cutting-edge research. The College is in the top group of UK universities for research earnings and has an overall annual income of approximately £450 million. An investment of £500 million has been made in the redevelopment of its estate.
King's has a particularly distinguished reputation in the humanities, law, social sciences, the health sciences, natural sciences and engineering, and has played a major role in many of the advances that have shaped modern life, such as the discovery of the structure of DNA. It is the largest centre for the education of healthcare professionals in Europe and is home to five Medical Research Council Centres - a total unsurpassed by any other university.
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 a world-leading Academic Health Sciences Centre (AHSC). Our AHSC 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.
About the Wellcome Trust
The Wellcome Trust is the largest charity in the UK. It funds innovative biomedical research, in the UK and internationally, spending over £600 million each year to support the brightest scientists with the best ideas. The Wellcome Trust supports public debate about biomedical research and its impact on health and wellbeing. www.wellcome.ac.uk
Professor Patricia Salinas, University College London
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