Encouraging early study for investigational drug in people with motor neurone disease

  • The University of Sheffield with Sheffield Teaching Hospitals NHS Foundation Trust is the only site in the UK to have participated in an, international clinical trial for an investigational drug in people with a form of motor neurone disease (MND)
  • Results from Phase 1-2 of the study sponsored by biotechnology company Biogen Inc. was published in the New England Journal of Medicine
  •  About 5,000 people in the UK have MND – also known as amyotrophic lateral sclerosis (ALS), with two per cent developing MND due to a faulty gene called SOD1
  • The disease affects motor neurons in the brain and spinal cord and progressively affects the ability to walk, talk, eat and breathe


Results from Phase 1-2 of a study published in the New England Journal of Medicine, have shown the safety and tolerability of the new investigational drug tofersen which shows the potential to reduce the levels of a toxic cell protein in people living with a form of motor neurone disease (MND); triggered by a faulty gene called SOD1 which causes the progression of the disease.

SOD1 is the known cause for triggering MND in two per cent of all patients with ALS, and up to 20 per cent of patients who have a family history of the disease.

Scientists from the University of Sheffield’s Institute for Translational Neuroscience (SITraN) worked with the Sheffield Teaching Hospitals NHS Foundation Trust on the study at the National Institute for Health Research (NIHR) Sheffield Biomedical Research Centre, the only site in the UK to participate in this exciting international clinical trial which evaluated the safety and efficacy of the investigational drug developed for SOD1 MND.

Amyotrophic lateral sclerosis (ALS), or motor neurone disease as is it known in the UK, is a disorder that affects the nerves - or motor neurons - in the brain and spinal cord that form the connection between the nervous system and muscles to enable movement of the body. The messages from these nerves gradually stop reaching the muscles, leading them to weaken, stiffen and eventually waste. The progressive disease affects a patient’s ability to walk, talk, use their arms and hands, eat and breathe.

Les Wood, 66, from Doncaster has been living with MND since 2012. He said: “I’m one of three siblings who all inherited the SOD1 gene and was in my mid-50s when I started noticing symptoms. My sisters had both developed MND earlier and I saw how quickly their condition deteriorated. So the research into diseases like MND that is happening now is so important.”

Professor Dame Pamela Shaw, Director of SITraN, European Chief Investigator on the trial and Director of the NIHR Sheffield Biomedical Research Centre, said: “The rise of genetic screening in our clinic means that we can now identify the different genetic subtypes of MND, which is helping to enhance the research effort.

“It has been a real privilege to participate in this trial of the investigational drug tofersen here in Sheffield, and our patients have shown huge commitment in taking part; so it’s a step forward that the published results warrant additional study in a larger patient group.”

Professor Chris McDermott from SITraN, Principal Investigator of the Sheffield trial and NIHR Sheffield BRC Deputy Director, said: “Superoxide dismutase 1, known as SOD1 was the first gene found to cause MND. It is an enzyme found in all living cells that acts as an antioxidant to reduce reactive oxygen species that would otherwise cause damage. About two per cent of people with MND have this mutation which causes the enzyme itself to be toxic to their cells.

“The primary objective of the study was to evaluate the safety and tolerability of tofersen which shows signs of potential efficacy in lowering the levels of the toxic SOD1 protein in the nervous system, something which will reduce damage in the nerve cells and help to slow the progression of symptoms."

The study also makes clear the reported adverse events, or apparent side effects, experienced by some of the participants such as headache, procedural pain, post-lumbar puncture syndrome and falls. Five tofersen, and two placebo-treated participants experienced serious adverse events.

One death occurred in the placebo group during the trial due to respiratory failure secondary to MND and two deaths occurred in the tofersen group during a follow up period due to pulmonary embolism and respiratory failure. The next phase of the trial will continue to further explore the safety and efficacy of the investigational drug.

Helen Wollff, Research Nurse on the Sheffield study based at SITraN, said: “It is a testimony to the research conducted at SITraN that Sheffield was the only UK site for the initial phases of the clinical trial. We look forward to the next stage of this clinical study sponsored by Biogen Inc. which will further evaluate the safety and efficacy of torfersen.”

Additional information

Read the full study

  • The research was supported by the NIHR Sheffield Biomedical Research Centre.
  • The research forms part of the work of the University of Sheffield’s Neuroscience Institute, which aims to bring academics and scientists together from across varied specialties to translate scientific discoveries from the lab into pioneering treatments that will benefit patients living with neurodegenerative disorders.

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, GlaxoSmithKline, Siemens and Airbus, as well as many UK and overseas government agencies and charitable foundations.

The National Institute for Health Research

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.

Acknowledgement of patient data

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.


For further information, please contact:

Rebecca Ferguson
Media Relations Officer
The University of Sheffield
0114 222 9859