Hope from a gene-targeted MND drug trial

You may have seen coverage of an ongoing clinical trial happening in Ireland, into a rare inherited form of motor neuron disease (MND), caused by changes to a gene known as Fused in Sarcoma (FUS). Early signs from the trial appear to be positive with one participant even reporting return of movement.

Belfast-born actor Michael Campbell, known professionally as Michael Patrick, was diagnosed with MND in February 2023 at the age of 35. Within a year of diagnosis, Michael was using a wheelchair, and he is now experiencing increasing weakness in his arms and breathing muscles. 

Michael has a specific form of familial (or inherited) MND called FUS-MND, which is caused by mutations in the FUS gene. Familial forms of MND, where faulty genes interfere with how nerve cells function and survive, account for around one in ten cases and incidences of FUS make up a small percentage of that number. FUS MND particularly affects younger people and is typically a rapidly progressing form of the disease. Both Michael and his sister, who also has MND, carry the same FUS gene variant and are enrolled in the same gene-targeted trial. 

The clinical trial is sponsored by Ionis Pharmaceuticals and is being delivered across many sites globally, including Dublin where Michael is taking part. The trial is testing a gene therapy (called an antisense oligonucleotide) that reduces the production of the FUS protein. To find out more about gene therapies, see our infographic here.

After spending the first 16 months of the trial on a placebo, the article says that Michael has now received several doses of the active drug. For the first time in more than two years, he has noticed a return of sensation and small movements in his feet.

In MND, small changes like this matter. Loss of function is usually permanent, so any sign of regained movement is unusual and very promising. Similar regained movement has also been reported by some participants of the Tofersen study, suggesting that when we get the right drug we can start to reverse disease. While it is still too early to draw firm conclusions, this early report suggests that the drug may be having a biological effect for Michael, but more data from more participants is needed to see a fuller picture.

Professor Orla Hardiman, Professor of Neurology at Trinity College Dublin and Consultant Neurologist at Beaumont Hospital, is leading the delivery of the trial in Dublin. Professor Hardiman has described the findings as “cautiously optimistic”, noting that regained movement in MND is rare and deserves close scientific attention.

We are currently funding two studies to develop FUS gene therapies that offer the potential to improve on the therapy that is being tested in this trial.

• Dr Younbok Lee at King’s College London, co-funded by MND Association, is developing an AAV gene therapy targeting FUS. If this approach is successful it would mean that the treatment only has to be administered once, whereas antisense oligonucleotides like the one in this study require repeat administration via multiple hospital visits.
• Dr Thomas Cunningham at UCL and his colleagues in Australia are developing an innovative antisense oligonucleotide gene therapy that unlike the therapy in this study only targets the mutated version of the FUS gene (everyone has two copies of the FUS gene, but only one copy needs to carry a mutation for the person to be affected by MND) so is thought to have fewer toxicities and a longer duration of effect meaning less frequent administration.

Michael’s story also shows why research matters. With virtually no treatment options available, potential therapies like this offer real hope that answers will be found that can slow, stop and even reverse MND.

Our Director of Research, Jessica Lee, said: “It suggests that if we understand the cause and biology of MND, we can develop effective treatments to address it, which is why more research to better understand MND biology in non-familial (sporadic) cases is so important. We’re proud to fund this kind of research, as well as the development of many other potential treatments that are currently being developed by our researchers all across the country.”

At My Name’5 Doddie Foundation, we know that breakthroughs do not happen overnight. Progress comes through rigorous trials, deep biological understanding and sustained funding. It is important to remember that this trial is still ongoing, but it is always exciting to hear of potential progress.