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A clinical trial of Jedi proportions…

The MND Association is backing a new clinical trial in MND, known as MIROCALS. This will be a joint clinical trial between France and the UK that will aim to dampen the overactive immune system by increasing the amount of interleukin-2.

It is important to stress that planning for this MND clinical trial has only just started and the next step is to lay the essential groundwork and perform some short-term pilot studies. The main trial is likely to begin recruiting participants in autumn 2016.

Cell Wars: The Force awakens

2015 sees the continuation of the hugely successful Star Wars films, which centres around the mysterious power of ‘The Force’ and how it can be used for both good and evil. The dark side of The Force can lead to disruption and death, whereas the good side (led by Jedi Knights) focuses on hope and life.

This intergalactic Star Wars battle is also taking place within the body (Cell Wars!). However, in MND, the dark side of The Force is unfortunately taking hold and causing the motor neurones to die. But, there is new hope. Researchers have designed a potential treatment that causes the return of the Jedi, leading to the good side of The Force fighting back!

Bluffers guide to Star Wars

We understand that some people may not be aware of the key players in the Star Wars films, but they’re a great way of explaining how the drug in MIROCALS, Interleukin-2 (IL-2) works. So, to help understand this blog post, we’ve outlined the main characters below:

• The Force – is a binding metaphysical invisible power that can be used for both good and evil (the ‘dark side’).
• Jedi – they have the knowledge and wisdom of the force to protect others and use it for good. Their chosen weapon is a lightsaber (our regulatory T-cell).
• Jedi Master – they have higher knowledge and wisdom of The Force allowing them to train new Jedi
• Yoda – a Jedi Master (Interleukin-2)
• Clone army – a human soldier that has been cloned to create a good army, which is under the command of the Jedi (our immune cells)

The dark side of MND

In MND the motor neurones get sick, losing their ability to communicate, which causes progressive muscle weakness. How MND causes motor neurones to die is still a bit of a mystery, however researchers have identified a number of processes that go wrong in motor neurones (you can read more about these on our website here).

A common process is ‘neuroinflammation’ or an increase in the number of immune cells surrounding the motor neurones. Usually, these immune cells are our clone army, tackling any invaders that may cause us harm (eg cold viruses). However in MND, these immune cells become out of control and begin to ‘switch’ to the dark side. When this happens, our immune cells begin to fight the motor neurones, mistaking them for enemy invaders.

The return of the Jedi

This switching of our immune cell clone army to the dark side happens because our own Jedi, who usually bring calm and peace, are missing in action.

Our immune cell clone army is usually controlled by a regulatory T-cell (in our Star Wars analogy, these are our Jedi). Our Jedi regulatory T-cells usually restore order and prevent our immune cell clone army from attacking unnecessarily.

However, in MND, the regulatory T-cells become low in numbers and faulty – they no longer have their light sabers! This means that our immune cell clone army goes unchecked, making it easily influenced by the dark side.

To restore order, a true Jedi Master is needed.

Enter Master Yoda

In MND our Jedi regulatory T-cells need some serious help. They need training to increase their numbers, as well as to develop their knowledge of The Force. Therefore, Master Yoda is needed to pass this knowledge on and ultimately increase their numbers.

Master Yoda comes in the form of IL-2 a cytokine, or chemical messenger, that is able to talk to the regulatory T-cells. If we can increase the amount of IL-2 (or Master Yoda) then potentially we could switch the power back to the good side of The Force, with our Jedi regulatory T-cells back in power, and our destructive immune cell clone army neutralised.

MIROCALS

This is where the Modifying Immune Response and Outcomes in Amyotrophic Lateral Sclerosis (MIROCALS) comes in. By working together, this Anglo-French MND clinical trial will aim to restore the Jedi order and conquer the dark side of The MND Force by increasing the amount of IL-2.

This clinical trial will aim to take place in the UK and France in autumn 2016.

This joint project between France and the UK, is supported by an award of €6million from the European Commission, with additional funding of €0.5million from the French government and a further €0.5million currently under consideration from the MND Association.

The two leaders behind this project are renowned MND researchers Prof Nigel Leigh (Brighton and Sussex Medical School) and Dr Gilbert Bensimon (Hôpital Pitié-Salpétrère, Paris). Both were involved in the development of Riluzole and, along with other leading MND researchers, make up the MIROCALS Consortium.

Director of Research Development at the MND Association, Dr Brian Dickie, said: “The Association is delighted to be involved in this clinical trial, which brings together two leading clinical researchers who both have a wealth of experience in designing and implementing clinical trials in MND.

“Since interleukin-2 is already well studied, we can monitor the effect of the drug on the immune system using well-defined biomarkers that will allow us to ‘individualise’ responses to treatment, as well as study some of the new biomarkers that have been linked to disease progression. This work will be done by leading MND biomarker researchers in the UK, Italy and Sweden.”

The next steps?

Prof Leigh and Dr Bensimon will begin working on the essential groundwork from September 2015, including a small pilot study in France, before the main trial can begin recruiting participants in autumn 2016.

Prof Leigh said: “The next step is to lay the essential groundwork for the study (Sept 2015-Aug 2016), which involves obtaining all the required Ethical and Regulatory approvals; appointing the researchers who will be working on the trial and on the laboratory experiments. The researchers will also need to put in place supplies of IL-2 and all the logistics for delivering the active treatment, and the placebo.

“It is important to stress that this MND clinical trial has only just started. The trial will begin recruiting the 216 people living with MND to take part in Autumn 2016 – although it may be possible to bring this forward if all goes well in the set-up stage.”

• Read the MND Association MIROCALS news story on our website
• Brighton and Sussex Medical School news story
• Read more about the research we fund

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MIROCALS project has received funding from the European Union’s Horizon 2020 research and innovation programme under grant agreement No 633413.

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