New study suggests genetic testing could be appropriate for all motor neuron disease (MND) patients whether or not they have a family history of the disease

• Researchers from the University of Sheffield undertook targeted genetic sequencing on 100 prospective MND 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 MND could improve our knowledge of disease classification and impact clinical care.
• MND - 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 MND patients and could impact disease subclassification and clinical care.

The new study, published today (15 February 2021) in the Journal of Neurology, Neurosurgery and Psychiatry (JNNP), performed targeted genetic sequencing of MND-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 MND patients whether or not they have a family history of the disease.

While the majority of MND 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 MND, 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 MND 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 MND-linked genes. This doesn’t mean that 42 per cent of MND 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 MND. Of these, 93 per cent had no family history of MND and 15 per cent met the inclusion criteria for a current MND gene therapy clinical trial.”

“As future studies expand the number of verified genetic causes of MND, 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 MND should, with careful counselling, be offered genetic testing.”

“We hope that by screening all MND patients for gene mutations that are a known factor in MND, 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 MND 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 “MND 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 MND Association funded project. This will provide an even clearer picture of the UK MND genetic landscape.’’

MND - 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 MND and no effective treatments to halt or reverse the progression of this devastating disease.

About NIHR Sheffield Biomedical Research Centre

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• Funds, supports and delivers high quality research that benefits the NHS, public health and social care
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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