New and effective treatments for MND are urgently needed and many scientists around the world are working towards this. Throughout 2024, we saw many new clinical trials beginning across the globe as the pace of MND research continued to grow. This momentum is continuing into 2025, with new clinical trials set to begin and plans for results to be announced. In this blog we will highlight some of the most anticipated updates from MND clinical trials happening in the UK that we are expecting this year.
UK trials expecting results this year
TRUST trial of Terazosin
Terazosin is a drug which is already licensed to treat high blood pressure. Early research in the laboratory has suggested that, in models of MND, Terazosin protected motor neurons and improved their survival. These results led to a small feasibility trial to investigate the benefits of Terazosin in people with MND.
This small study involved researchers monitoring levels of a marker of neuron damage, called neurofilament light chain, in people throughout the trial. Research has shown that neurofilament light chain levels are raised in people with MND, as more neurons are damaged. Reducing the levels of neurofilament light chain could suggest less damage is happening to motor neurons and that a treatment is having a beneficial effect. Top-line results from the trial are expected in the coming months. These results will help to decide whether Terazosin should be tested in larger clinical trials.
MND-SMART trial of Amantadine
MND-SMART is the UK’s first platform trial in MND. It is designed to test more than one potential treatment at a time and is adaptive, meaning that researchers can change the drugs being tested throughout the trial, allowing new ones to be added and removing those that are found to have no benefit.
One of the drugs being tested through the trial is Amantadine, which is already used in the management of Parkinson’s disease, treatment of fatigue in Multiple Sclerosis and as an antiviral medicine in the treatment of a type of influenza. It is thought that I could help to reduce the abnormal clumping of the TDP-43 protein which occurs in around 97% of people with MND.
MND-SMART is designed with regular monitoring in place for each drug to assess whether to continue testing that drug. This means that drugs which aren’t showing positive signs can be removed at specified time points during the trial. For each drug tested in the trial there are four time points where the data collected is reviewed by a committee. The first stage analysis of Amantadine was completed in December 2024 and the committee concluded that the testing should continue. Further analysis from the testing of Amantadine is expected this year.
DAZALS trial of Dazucorilant- Open Label Extension Results
Dazucorilant is a drug which was designed to block a protein which normally binds to a chemical in the brain called cortisol. Increased levels of cortisol have been seen in people with MND and high levels of cortisol have been shown to increase inflammation and be toxic to nerve cells. Dazucorilant blocks a protein which normally binds to cortisol. Blocking cortisol from binding is thought to limit the consequences of increased cortisol and potentially help slow disease progression. In early laboratory testing, Dazucorilant was found to improve motor performance, reduce neuroinflammation and muscle wasting.
Topline results from the DAZALS trial were announced in 2024, which found that the trial did not meet it’s primary endpoint. There was no significant change in ALSFRS-R (from baseline to 24-weeks) for those who received the treatment compared to those who received the placebo.
Everyone who took part in the trial was given the chance to enter an open label extension, where everyone is given the drug for a period of time. Open label extensions can help to see if the drug shows signs of benefit over a longer period of time than the duration of the trial. Results from the open label extension of the DAZALS trial are expected in the coming months.
MIROCALS trial of Interleukin-2- Full anaylsis of data
Inflammation is thought to influence the spread of damage throughout the brain and spinal cord and this has been linked to the speed of progression in MND. Our bodies can help to control inflammation through a type of immune system cell called a Regulatory T Cell (Treg). Research has shown that Interleukin-2 (IL-2) can help to control Tregs and low doses of the drug can increase the number and function of Treg cells in the blood. MIROCALS (Modifying Immune Response and OutComes in ALS) was a phase 2 trial which investigated the impact of IL-2 on disease progression and survival.
Topline results from the trial were announced in 2022, which suggested that IL-2 may have a potential survival benefit for certain people living with MND. You can read about these results here. Since these topline results were announced, the researchers have been working to complete the full analysis of the data. The full results are expected to be published in 2025. You can see our latest update on our website.
UK trials increasing recruitment this year
MND-SMART
As well as being expected to release results this year, MND-SMART is expected to continue testing drugs that show promise for treating MND. The platform trial is designed to test more than one treatment at a time and has already tested two drugs (Memantine and Trazadone) , with testing of a third (Amantadine) continuing into 2025. The trial drugs can be changed throughout the trial as new ones can be added and ones that are found to have no benefit can be removed. The first two drugs were removed from the trial as they were found not to be effective at slowing disease progression.
MND-SMART will continue recruiting participants throughout 2025 as new drugs are expected to be added in the next few months. There are also plans to open five new trial sites this year. Both of these additions will mean that more people with MND will have the opportunity to take part in the trial.
RELATED POST
Blog | 19 June 2023 | Eleanor Green
Keeping MND-SMART moving
EXPERTS-ALS
EXPERTS-ALS is a platform which aims to rapidly test drugs to assess their potential to slow MND progression. The platform will test multiple drugs at the same time that have shown promise for treating MND in the laboratory. The study will measure a marker of neuron damage within the body, called neurofilament light chain (NfL), to see if the treatment is found to significantly reduce levels of NfL. If the treatment is found to significantly reduce levels of NfL across the whole group of participants it suggests there are early signs of benefit and it should be priortised for further testing in a larger clinical trial.
The platform opened for recruitment in November 2024 and there are now seven sites across the UK that are running the study. A further four sites are still in the set-up stages and hope to open in the coming months, meaning that more people will have the chance to take part in the study.
RELATED POST
Blog | 21 June 2023 | Eleanor Green
EXPERTS-ALS: a new drug testing platform from the UK MND Research Institute
There are other clinical trials that are currently recruiting in the UK and you can find out more about these on our website.
With so many clinical trials for MND happening across the globe, we know it can be hard to keep up to date with them all! We hope that this blog has helped to give you a snapshot of the UK clinical trial updates that we’re expecting this year. You can find more information on the latest news in MND research on our website.
Look out for part 2 of this blog series where we’ll highlight clinical trials that are happening internationally that you might want to keep an eye on in 2025!
