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Research visit: Professor Janine Kirby

06 February 2023

Jessica Lee, Director of Research, and Olivia Bird, Research Programme Manager, recently visited the Sheffield Institute of Translational Neuroscience (SITraN) to meet Professor Janine Kirby, whose work has been supported by My Name’5 Doddie Foundation for several years.

Professor Kirby’s work is linked to the MIROCALS clinical trial, which tested low-dose interleukin-2 (IL-2) in combination with riluzole in people with motor neuron disease (MND). IL-2 modifies the immune system by increasing the number of a specific type of cell, called a “regulatory T-cell”. In people with MND, regulatory T-cells are often reduced in number, or they don’t work as they should, causing overactivation of the immune system that can damage motor neurons and contribute to the progression of the disease. By increasing the number of regulatory T-cells, it is hoped that the motor neurons will be protected and disease progression will be slower. 

The first results of MIROCALS were presented last month at Motor Neurone Disease Association’s 33rd International Symposium on ALS/MND. IL-2 did not significantly impact survival when researchers analysed the trial population as a whole, however, sub-group analysis revealed that the drug could slow the disease in a subset of participants. In people with a low-moderate level of a biomarker (called neurofilament heavy chain) at the start of the trial, there was a decrease in risk of death at 21 months of over 40%.

The Foundation has supported the post of a Research Technician, Alex Daniel, to carry out work that will help us understand why different people responded differently to the trial drug.

What work is being carried out?

Alex has been extracting genetic material from the white blood cells of participants of the MIROCALS trial who kindly donated blood samples during the course of the trial. Each participant donated 5 samples - that’s over 800 samples to analyse!

Using a technique called gene expression profiling Janine and Alex can begin to understand which genes are switched on and which are switched off in response to the treatment. To find out more about gene expression profiling, see our infographic below.

The trial was ‘blinded’ meaning neither the participants, healthcare teams nor researchers know who was receiving the active drug and who was receiving the placebo (dummy drug). This ensures that all samples are treated in the same way and there is no bias in the analysis of results. Which group the samples belong to is only revealed once the analysis is complete.

What impact will this have?

Using the gene expression profiles from the trial participants, Janine and her colleagues will look to answer many questions, including:

  • How do different genes respond to IL-2?
  • Why do some people respond better to IL-2 than others?
  • What does the gene expression profile tell us about people with high vs. low levels of neurofilament heavy chain?

What’s more, participants also donated samples before starting the trial drug/placebo, so this analysis will also shed light on the gene expression changes in response to riluzole as well as IL-2. This may be beneficial to not only improve riluzole as a treatment for MND but also for the future development of new treatments that target the same pathways as riluzole.

This investigation into the gene changes associated with IL-2 would not be possible without the generous participants of the MIROCALS trial who donated samples for future research. We would also like to thank our supporters whose funding has allowed us to increase our understanding of this treatment and may help us in the push towards more personalised treatments for MND.

Finally, we offer huge thanks to Professor Janine Kirby and Alex Daniel for their immense contributions to the analysis of MIROCALS samples and for their ongoing support in helping us to achieve our vision of a world free of MND.

Read more about the immune system and MND in our article about our visit to Professor Tim Tree here.

Research visit: Professor Janine Kirby
Research visit: Professor Janine Kirby

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