A groundbreaking phase 3 clinical trial that was testing against a rare form of motor neurone disease (MND) has made a major breakthrough, thanks to research from the University of Sheffield.
The trial, conducted by researchers from Sheffield Institute for Translational Neuroscience (SITraN), found that patients with a defective SOD1 gene realised that the progression of their symptoms slowed down approximately 12 months after taking the experimental drug tofersen.
Although no physical benefits were reported after six months, results from the trial did reveal that at the original endpoint of the study, the biomarkers in the patients’ spinal fluid showed a reduction in SOD1 and neurofilament protein levels, suggesting that tofersen was reducing the loss of motor neurones, potentially allowing them to regenerate muscle connections and regain mobility.
It was only after the researchers initial six month discovery that the trial was extended, enabling the research to further discover that patients experienced physical benefits from the drug after 12 months.
Professor Dame Pamela Shaw, Professor of Neurology and Director of SITraN at the University of Sheffield, 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.”
“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.”
More than 100 patients with the faulty SOD1 gene participated in the landmark trial – superoxide dismutase 1, or SOD1, is responsible for 2% of all MND cases and is the first gene to be linked to MND in this way.
Professor Chris McDermott, Professor of Translational Neurology at SITraN University of Sheffield and Co-Author of the study, said: “This is the first time I have been involved in a clinical trial for people living with MND where I have seen real benefits to participants.
“Although tofersen is a treatment for only 2% of those living with MND, we have learned much in doing this clinical trial that will help us do smarter and faster clinical trials in the future. The approach used, of reducing proteins harmful in MND, is likely to have wider applications for more common types of MND.”
Health professionals hope that this discovery is the first step towards a licensed therapy for MND patients.