Ask the Expert Recap: Clinical Trials in MND

11 May 2023

On Monday 6th March 2023, the Foundation’s Medical Strategy Lead, Sean McGrath hosted Professor Dame Pamela Shaw of the University of Sheffield and Foundation Ambassador Rob Wainwright, in conversation about clinical trials in MND. If you missed the session, don’t worry! You can watch it again at the bottom of this page, but we have summarised the key points in this article.

The MND Clinical Trial Landscape: Then and Now

Professor Shaw began the session by assuring us that the MND clinical trial landscape has changed enormously over the last few years. In the past, only one trial would run at a time, academic-led trials were rare, and the number of people who could participate in a trial was limited.

Now, partly helped by My Name’5 Doddie Foundation, the landscape looks very different.There are over 500 people on the MND-SMART trial alone, and two recent trials in particular, VALOR and MIROCALS, have shed light on the best way to conduct trials, providing hope and confidence for the future. We have also started testing drugs that are already licensed elsewhere to see if they offer any benefit to people living with MND. What’s more, with the development of biomarkers, we have a greater ability to monitor whether drugs are having an effect. 

A spotlight on VALOR 

Last year we reported on the outcome of the VALOR trial, a phase 3 clinical trial of tofersen, a genetic therapy for people with SOD1-MND. Professor Shaw tells us, of 23 trials of MND that she has been involved in over her career, VALOR is the first one in which some participants have shown not only stabilisation of their condition, but for some people, improvements. In fact, on 25th April 2023, the US FDA approved tofersen to treat SOD1-ALS, based on the biomarker data that showed tofersen lowered neurofilament levels in the blood. Biomarkers have been used to monitor other diseases for decades e.g. a measure of inflammatory lesions in multiple sclerosis can tell you how the disease is progressing. We haven’t had this in MND before; we’ve had to rely on things like disability rating scales. Biomarkers have led to huge developments in other disease areas and now have the potential to change the MND landscape too.

Biomarkers for earlier diagnosis

Professor Shaw tells us that, on average, it takes 12 months from an individual first noticing symptoms of MND before they are seen in a neurology clinic. That’s because, until now, diagnosis of MND has been more of a process of elimination of other conditions, than a definitive set of investigations for MND. However, with the recent discovery of neurofilament as a potential marker for damaged neurons, she hopes that one day a clinical service could be set up to measure neurofilament as soon as an individual presents with symptoms of MND, so that, if they are elevated, they can be fast-tracked to a neurology clinic.

Clinical trials for pre-symptomatic gene carriers

In response to the VALOR trial that showed people who took tofersen earlier in their disease course did better than those who started tofersen later, the ATLAS trial was started. In this trial, people with a known SOD1 mutation but not showing any signs of MND, will have their neurofilament levels monitored regularly. If and when neurofilament levels begin to increase, which may be before the onset of other symptoms of the disease, the individual will begin treatment with tofersen. By monitoring ‘pre-symptomatic’ disease in this way, it is hoped that the earlier the treatment is started, the better the outcome will be.

Re-purposing trials

A huge advancement in the ability to screen drugs for trials is the ability to re-programme human skin cells into motor neurons (induced pluripotent stem cells) in a lab. Whole libraries of approved drugs can then be efficiently screened in these motor neurons to identify any that may protect motor neurons against MND (at Professor Shaw’s institute, SITraN, researchers have access to a library of over 500 FDA-approved drugs, which can all cross the blood brain barrier to reach the central nervous system where the motor neurons are located). This has dramatically improved the pipeline of drugs that are being progressed into clinical trials.

One of the repurposing trials that is currently ongoing and being supported by the Foundation, is MND-SMART. Led by the Euan MacDonald Centre at the University of Edinburgh, it’s what’s known as a platform trial in which multiple drugs can be tested against a single placebo group, thus reducing the number of people with MND who are on placebo. You can read more about platform trials here.

How to get involved in a clinical trial

Professor Shaw urges anyone living with MND who is interested in taking part in a clinical trial to be assertive with and raise this matter with their GP and local neurologist. If you have any questions about clinical trials please get in contact with the Foundation at research@myname5doddie.co.uk.