ALS is the most common form of MND and these terms are used interchangeably in this blog.
The pace of MND research continues to increase, with more clinical trials underway in the UK, over the last year, than ever before. Adding to this momentum, the clinical platform trial MAGNET (Multi-arm, Adaptive, Group-sequential trial NETwork) has just opened to recruitment in the UK.
Over the last several decades, there have been over 140 clinical trials for MND and unfortunately most of these have not led to effective treatments. More recently, clinical trial design has become more innovative, including the use of platform trials. MAGNET is a platform trial which aims to accelerate the development of new potential treatments for MND by testing multiple drugs simultaneously.
What is a platform trial?
Unlike a regular double-arm control trial which tests one drug vs placebo, a platform drug trial can test multiple drugs simultaneously. This aims to accelerate the development of new treatments by reducing the cost and logistical challenges that go into setting up and running individual trials. Another a major advantage of platform trials is that the multi-arm design means there is a higher proportion of people randomised onto a treatment and less are randomised to the placebo.
Platform trials also aim to enhance the number of people who are eligible to take part in trials. Many clinical trials have strict criteria which must be met in order to be accepted onto the trial. This results in many people living with MND being excluded. MAGNET aims to give more people living with MND access to participate in clinical trials.
The MAGNET trial uses a computer model which determines whether you are eligible to participate, based on your disease characteristics such as age, symptom duration and lung function. The computer then makes a forecast of the expected disease pattern. By using this forecast, more than 75% will be able to participate instead of the 25 – 40% when using classical criteria.
“The TRICALS computer model can in some cases increase the number of eligible participants five-fold. It also means we can test investigational drugs in a more diverse patient population. The ultimate goal is to give everyone living with ALS the chance to participate in clinical trials.”Dr Ruben van Eijk, assistant professor and medical statistician at UMC Utrecht.
Globally, there are now three platform trials underway that are testing potential treatments for MND. This includes the HEALEY Platform trial in the United States, MND SMART in the UK, and MAGNET in Europe and Australia.
Which drugs are being tested in MAGNET?
The first drug to be trialled on the MAGNET trial is lithium carbonate, with additional drugs to be added in the future.
Hasn’t lithium carbonate been tested before?
Over a decade ago, there was some buzz around lithium carbonate as a treatment for MND. In 2012, the MND Association funded LiCALS, a UK-based clinical trial which tested lithium carbonate in a varied group of people living with MND. This trial failed to meet its primary end points and showed that lithium did not show any benefit for people living with MND. So why is lithium carbonate now being revisited?
Since this trial, we have made leaps in our understanding of MND and the underlying genetic factors which play a role in its cause and progression. This led researchers to go back over the data from the original trial to look for any hints or clues that lithium carbonate could be beneficial for certain genetic types of MND. They found that there was potentially a beneficial effect observed for those on the trial who were given lithium carbonate AND had a particular change (also known as variant) in the UNC13A gene.
This effect was also found in two other clinical trials which investigated lithium carbonate in MND. Now, in order to confirm these findings, lithium carbonate needs to be tested in a clinical trial which only recruits people with MND who have a change in the UNC13A gene.
Blog | 13 October 2017 | Dr Brian Dickie
Lithium revisted: Is there a baby in the bathwater?
How is lithium carbonate proposed to work in MND?
Lithium carbonate has a long history as a treatment for mood disorders and several studies have highlighted that lithium carbonate has protective effects in the brain. It is also described as a ‘messy drug’, meaning it can act in multiple ways in the body. Currently, it is not known how exactly lithium interacts with the UNC13A gene/protein to show this potential benefit.
How do I find out if I have the UNC13A gene?
Changes in the UNC13A gene are found in around one out of six people living with MND. At the moment the UNC13A gene is not routinely tested for outside of research. This is because changes in the UNC13A gene are a “risk factor” for MND, not a genetic cause. This means that a change in the UNC13A gene can help to predict a person’s risk for developing the disease. The UNC13A gene is also thought to impact the progression of the disease, often resulting faster progression.
When people register their interest to take part in clinical trials, they are screened to check that they are eligible for the trial. Genetic testing for the UNC13A gene will take place during the screening phase of MAGNET.
How can I get involved in the clinical trial?
The MAGNET platform trial is a multi-centre trial, which will be recruiting in the UK, Europe and Australia. It is currently recruiting in the UK at the following site:
- King’s College London – please contact Senior ALS Clinical Trials Manager Theresa Chiwera on firstname.lastname@example.org for more information.
Additional sites are expected to open in the UK soon. For more information and to keep updated on new sites as they open, please head to the MAGNET page on our website.
Website | Clinical Trials
Find out about treatment trials recruiting in the UK
With more clinical trials recruiting in the UK than ever before, we are so grateful for the dedication, generosity and commitment of the researchers, healthcare professionals and people living with and affected by MND. Without the support of the whole MND community trials such as MAGNET would not be possible and new potential treatments for MND would not be found.
We are also so thankful for everyone who has generously supported the MND Association. Your support enables us to fund the most promising and cutting-edge research in the fight against MND.
MAGNET has been formed through the collaboration of TRICALS (The Research Initiative to Cure ALS) with foundations and funding agencies in Europe and Australia, including the MND Association. You can find out more on the TRICALS website.
Our thanks to the Greendale Foundation, P F Charitable Trust and the Payne-Gallwey Charitable Trust who have supported this project.
* The information in this blog was correct at the time of publication