51��ݶ�

• Researchers from the University of Sheffield undertook targeted genetic sequencing on 100 prospective 51��ݶ� patients.
• The study, funded by the Motor Neurone Disease Association, found higher than expected genetic changes in this group of patients.
• Offering routine genetic testing for 51��ݶ� could improve our knowledge of disease classification and impact clinical care.
• 51��ݶ� - also known as Amyotrophic Lateral Sclerosis (ALS) - is a devastating disease that affects 5,000 people in the UK and 450,000 people worldwide.

Research from the Sheffield Institute for Translational Neuroscience (SITraN) suggests that routine genetic testing may be appropriate for all 51��ݶ� patients and could impact disease subclassification and clinical care.

The , published today (15 February 2021) in the Journal of Neurology, Neurosurgery and Psychiatry (JNNP), performed targeted genetic sequencing of 51��ݶ�-relevant genes on 100 patients.

Researchers found higher than expected genetic changes in the group of patients. The paper recommends that genetic testing could be appropriate for all 51��ݶ� patients whether or not they have a family history of the disease.

While the majority of 51��ݶ� cases are considered sporadic, five per cent to 10 per cent have been shown to be familial. Currently only patients with a family history of 51��ݶ�, dementia, or who experience disease onset at a young age are routinely offered genetic screenings in the UK. However, with the development of new therapies targeting specific genetic forms of the disease, researchers are recommending that all 51��ݶ� patients are offered a screening.

Prof Janine Kirby, Professor of Neurogenetics at the University of Sheffield, said “Our study found that 42 per cent of patients involved in the screening showed variants in known 51��ݶ�-linked genes. This doesn’t mean that 42 per cent of 51��ݶ� cases are familial - but shows that some familial and sporadic cases can share the same genetic cause of disease.”

“We found that 21 per cent of patients had a clinically reportable genetic alteration that has been proven to increase the likelihood of developing 51��ݶ�. Of these, 93 per cent had no family history of 51��ݶ� and 15 per cent met the inclusion criteria for a current 51��ݶ� gene therapy clinical trial.”

“As future studies expand the number of verified genetic causes of 51��ݶ�, we will continue to see if they are also found in cases without a family history.”

Professor Dame Pamela Shaw, Director of SITraN and the NIHR Sheffield Biomedical Research Centre said “Our study suggests that all patients with 51��ݶ� should, with careful counselling, be offered genetic testing.”

“We hope that by screening all 51��ݶ� patients for gene mutations that are a known factor in 51��ݶ�, we can further our knowledge on subclassification of the disease, but also ensure that patients have access to clinical trials that are relevant for them personally."

“This is increasingly important in light of the new personalised medicine treatments in development for 51��ݶ� that target a specific gene mutation to ensure that patients have access to potential treatments that could be beneficial to them.”

Dr Brian Dickie, Director of Research Development at the Motor Neurone Disease Association said “51��ݶ� is a complex disease involving a complex mix of genetic and environmental factors. This latest research sheds more light on the genetic component and will hopefully lead to greater availability of genetic testing to aid earlier diagnosis and more tailored treatments in the future.”

“This study was supported by funds raised through the Ice Bucket Challenge and will be widened to include analysis of additional samples from two other clinics collaborating on this 51��ݶ� Association funded project. This will provide an even clearer picture of the UK 51��ݶ� genetic landscape.’’

51��ݶ� - also known as amyotrophic lateral sclerosis (ALS) - is an adult-onset neurodegenerative disease characterised by progressive injury and cell death of upper and lower motor neurons. This leads to progressive failure of the neuromuscular system with death, usually from respiratory failure, within 2–5 years of symptoms in most cases.

Currently, there is no cure for 51��ݶ� and no effective treatments to halt or reverse the progression of this devastating disease.

51��ݶ� NIHR Sheffield Biomedical Research Centre

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. www.nihr.ac.uk/patientdata