A new genetically targeted MND therapy could be a game-changer for patient care

A new genetically targeted MND therapy could be a game-changer for patient care

Scientists believe a new genetically targeted therapy to treat motor neuron disease (MND) could be a game-changer for patient care after 12-month results from a Phase 3 clinical trial showed significant physical benefits for patients.

Researchers at the Sheffield Institute for Translational Neuroscience (SITraN) found that patients with a faulty SOD1 gene - which accounts for two per cent of MND cases - noticed the progression of their symptoms slowed 12 months after taking the investigational drug tofersen.

108 MND patients known to have the faulty SOD1 gene took part in the groundbreaking Phase 3 clinical trial, funded by biotechnology company Biogen Inc. Although no significant clinical improvement was noted in the study's primary endpoint at 28 weeks, the study was extended until week 52 and notable changes in patients' motor function and pulmonary function were reported.

The results of the study, published in the New England Journal of Medicine, show that biomarkers in the patients' spinal fluid showed a reduction in SOD1 and neurofilament protein levels after six months of taking tofersen, suggesting that the treatment successfully achieves the therapeutic goal and reduces loss of motor neurons, which could allow them to form connections with the muscles in the body regenerate. However, it took longer for patients to experience reported physical improvements.

I have conducted more than 25 MND clinical trials and the Tofersen trial is the first trial in which patients have reported improvement in their motor function. I've never heard patients say, "I'm doing things today that I couldn't do a few months ago - walking around the house without canes, going up the garden stairs, writing Christmas cards." For me, this is an important treatment milestone.”

Professor Dame Pamela Shaw, Professor of Neurology and Director of SITraN, University of Sheffield

Dame Pam added: "We have found that we can reduce or slow down biological damage, but the motor neurons need more time to heal and regenerate their connections with the muscles. So the motor system needs time to heal before we see any physical and clinical change.

"Patients with SOD1 mutations are relatively rare, but this study will change the future of MND trials for patients. Not only can we study other genes that also cause MND, but we now have a biomarker that we can measure to determine whether a treatment is working. This will make trials much more efficient. In the future, we may be able to determine in three to six months whether an experimental therapy has a positive effect shows."

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 with MND where I have seen real benefits for participants.” . Although tofersen is only a treatment for two percent of people with MND, we learned a lot from conducting this clinical trial that will help us conduct smarter and faster clinical trials in the future. The approach used to reduce harmful proteins in MND will likely have broader applications for more common types of MND.”

MND, also known as amyotrophic lateral sclerosis (ALS), is a disease that affects the nerves - or motor neurons - in the brain and spinal cord that form the connection between the nervous system and the muscles and enable the body to move. The signals from these nerves gradually stop reaching the muscles, causing them to become weaker, stiffer and ultimately weaker. The progressive disease affects the patient's ability to walk, talk, use their arms and hands, eat and breathe.

SOD1 is the known cause of triggering MND in two percent of all patients with ALS and in up to 20 percent of patients with a family history of the disease.

Dr. Brian Dickie, research director at the MND Association, said: "These latest results provide increasing confidence that tofersen has both a biological and beneficial clinical effect in people with SOD1-MND." They also provide an important “proof of concept” that similar gene therapy-based approaches may be helpful in other forms of the disease. We are closely following the recent news that tofersen is under review by the US drug regulatory authorities and are in contact with Biogen to discuss what the regulatory approval process will look like elsewhere.”

Clinicians and scientists hope this is a first step toward an approved therapy for MND patients.

Source:

University of Sheffield