News Release

New gene variation which causes MND discovered in novel biological pathway

Peer-Reviewed Publication

University of Sheffield

Scientists have discovered a new gene varitation that causes motor neurone disease (MND) in a novel biological pathway that until now hasn't been linked with neurodegeneration.

The findings for the pioneering study, conducted by team of researchers from the Sheffield Institute for Translational Neuroscience (SITraN) and the NIHR Sheffield Biomedical Research Centre (BRC), could potentially help to identify completely new ways of treating MND which currently affects over 5,000 people in the UK.

MND, also known as amyotrophic lateral sclerosis (ALS), is a devastating neurogenerative disorder that affects the nerves - motor neurones - that form the connection between the brain and the muscles.

The messages from these nerves gradually stop reaching the muscles, causing them to weaken, stiffen and eventually waste. The progressive disease affects a persons's ability to walk, talk, eat and breathe.

Approximately 10 per cent of MND cases are inherited but the remaining 90 per cent are caused by complex genetic and environmental interactions which are not well understood - this is known as sporadic MND. There is currently no curative therapy.

Dr Johnathan Cooper-Knock, NIHR Clinical Lecturer at the University of Sheffield's Institute forTranslational Neuroscience (SITraN) explained the impact of the groundbreaking research which is helping scientists to understand the fundamental genetic basis of MND.

"This new gene does not fit into a biological function that we already know is associated with MND, " said Dr Cooper-Knock.

"That means that this finding has potential to identify completely new ways of treating MND.

"The mutations found in patients were shown to be toxic to neurons and, when expressed in zebrafish they produced muscle weakness consistent with MND. This work strongly suggests that the mutations are the cause of MND in the patients where they were identified."

During the study, published today (26 February 2019) in the journal Cell Reports, researchers genetically sequenced tissue from two related patients with an unknown familial form of MND and found a mutation in the substrate binding region of a glycosyltransferase enzyme called GLT8D1. They went on to screen a larger sample of 103 patients, five of whom had this mutation. The study revealed a new genetic subtype of MND.

Professor Dame Pamela Shaw, Director of SITraN and the NIHR Sheffield BRC said: "Genetic screening of MND patients is becoming increasingly important as we subclassify the disease and look for new therapeutic strategies.

"MND is a devastating disease, and what we need is are more powerful therapies that protect motor neurons from injury and substantially slow down the progression of MND. Fundaamental science breakthroughs, such as the discovery of this new gene that causes MND, are vitally important in helping us to understand the mechanisms of disease; - paving the way to find potential new therapies."

"SITraN is one of the world-leading centres for research into MND. From basic neuroscience research pulled through to novel therapies and clinical trials, our aim is to improve the health and wellbeing of patients with MND and related neurodegenerative disorders and their families worldwide."

Tobias Moll who worked on the study under the supervision of Dr Cooper-Knock and Professor Shaw is completing a PhD with the NIHR Sheffield BRC Junior Academy. The NIHR Sheffield BRC is training 15 early career researchers supported by Clinical Fellowships and PhD Scholarships to work on translational neuroscience projects across chronic neurological conditions.

Tobias said: "It's great to be part of an Academy while doing my PhD. Through my clinical and scientific colleagues I get to see the wider context of my research. It is wonderful that I have had the opportunity to meet with patients whose medical condition I am working on, through the BRC and SITraN patient and public involvement groups.

This is really inspiring and helps me to see where my research really has an impact."

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For further information please contact: Amy Huxtable, Media Relations Officer, University of Sheffield, 0114 222 9859, a.l.huxtable@sheffield.ac.uk

Notes to editors

The University of Sheffield

With almost 29,000 of the brightest students from over 140 countries, learning alongside over 1,200 of the best academics from across the globe, the University of Sheffield is one of the world's leading universities.

A member of the UK's prestigious Russell Group of leading research-led institutions, Sheffield offers world-class teaching and research excellence across a wide range of disciplines.

Unified by the power of discovery and understanding, staff and students at the university are committed to finding new ways to transform the world we live in.

Sheffield is the only university to feature in The Sunday Times 100 Best Not-For-Profit Organisations to Work For 2018 and for the last eight years has been ranked in the top five UK universities for Student Satisfaction by Times Higher Education.

Sheffield has six Nobel Prize winners among former staff and students and its alumni go on to hold positions of great responsibility and influence all over the world, making significant contributions in their chosen fields.

Global research partners and clients include Boeing, Rolls-Royce, Unilever, AstraZeneca, Glaxo SmithKline, Siemens and Airbus, as well as many UK and overseas government agencies and charitable foundations.

The National Institute for Health Research (NIHR) Sheffield Biomedical Research Centre (BRC).

The NIHR BRC is a research partnership between the University of Sheffield and Sheffield Teaching Hospitals NHS Foundation Trust, dedicated to improving the treatment and care of people living with chronic neurological disorders.

The Sheffield Centre is one of 20 designated NIHR Biomedical Research Centres across the country, and hosts the development of new, ground-breaking treatments, diagnostics, prevention and care for patients with debilitating diseases such as dementia, motor neurone disease, stroke, multiple sclerosis, Alzheimer's and Parkinson disease.

For more information please visit: http://sheffieldbrc.nihr.ac.uk/

The National Institute for Health Research (NIHR)

The National Institute for Health Research (NIHR) is the nation's largest funder of health and care research. The NIHR:

  • Funds, supports and delivers high quality research that benefits the NHS, public health and social care
  • Engages and involves patients, carers and the public in order to improve the reach, quality and impact of research
  • Attracts, trains and supports the best researchers to tackle the complex health and care challenges of the future
  • Invests in world-class infrastructure and a skilled delivery workforce to translate discoveries into improved treatments and services
  • Partners with other public funders, charities and industry to maximise the value of research to patients and the economy

The NIHR was established in 2006 to improve the health and wealth of the nation through research, and is funded by the Department of Health and Social Care. In addition to its national role, the NIHR commissions applied health research to benefit the poorest people in low- and middle-income countries, using Official Development Assistance funding.

This work uses data provided by patients and collected by the NHS as part of their care and support and would not have been possible without access to this data. The NIHR recognises and values the role of patient data, securely accessed and stored, both in underpinning and leading to improvements in research and care. http://www.nihr.ac.uk/patientdata


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