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Promising motor neurone disease drug helps slow disease progression

Published: 22 September 2022

A landmark trial supported by NIHR researchers has found an experimental drug targeting a rare form of motor neurone disease showed significant physical benefits after 12 months.  

The phase 3 clinical trial, published in the New England Journal of Medicine, has shown that the new investigational drug tofersen can slow and reduce progression of the disease in patients with MND caused by the faulty SOD1 gene.

MND is a disorder that affects the nerves - or motor neurones - in the brain and spinal cord that form the connection between the nervous system and muscles, enabling movement of the body. In people with MND, the messages from these nerves gradually stop reaching the muscles, leading them to weaken, stiffen and eventually waste. 

About 5,000 people in the UK have MND. The progressive disease affects their ability to walk, talk, use their arms and hands, eat and breathe.

Superoxide dismutase 1, known as SOD1, is the first gene found to be linked to MND. Mutations in this gene in people with MND cause a normal enzyme to become toxic to nerve cells and cause progression of the disease. The SOD1 gene is the known cause in 2% of all MND patients. 

A previous phase 1-2 study showed tofersen is safe and well tolerated in people with this genetic form of MND.  

The phase 3 trial supported by researchers from NIHR Sheffield Biomedical Research Centre found that, though biomarkers in patients' cerebrospinal fluid showed improvement at six months, it took 12 months for identification of physical benefits. Sheffield was the major trial site in the UK and 108 patients took part in the phase 3 trial.

Professor Dame Pamela Shaw, Professor of Neurology and Director of the NIHR Sheffield Biomedical Research Centre, said: “I have conducted more than 25 MND clinical trials and the tofersen trial is the first trial in which patients have reported an improvement in their motor function. Never before have I heard patients say ‘I am doing things today that I couldn’t do a few months ago - walking in the house without my sticks, walking up the garden steps, writing Christmas cards’. For me this is an important treatment milestone.”

Dame Pam added: “What we have found is that we can reduce or slow damage from happening biologically, but it takes more time for the motor neurones to heal and regenerate their connections with the muscles. So, the motor system needs time to heal before we see a physical and clinical change.

 “Patients with SOD1 mutations are relatively rare, but this trial is going to change the future of MND trials for patients. Not only can we look at other genes which also cause MND, but we now have a biomarker which we can measure to see if a treatment is working. This is going to make trials much more efficient. In future we may be able to tell in three to six months if an experimental therapy is having a positive effect.”

Although tofersen is a treatment for only two per cent of those living with MND, the approach used, of reducing proteins harmful in MND, is likely to have wider applications for more common types of MND.


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