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Research

Project Summaries for Sussex MND Care & Research Network

Amyotrophic lateral sclerosis (ALS; MND, motor neuron disease) is a progressive degenerative disease of motor neurons in the brain and spinal cord affecting about 4000 people each year in the UK. There is no cure for ALS and although genetic factors cause about 10% of cases, for most people the cause is unknown.

BACKGROUND IMAGE FOR PANEL

MIROCALS study and Interleukin II

Update July 2023: This study is now complete, and the results will be published soon.

There has been lots of coverage in the press and social media about the results of the MIROCALS study and potential licencing of Interleukin II as a treatment for MND.

The MND Association have created an access to treatment taskforce and produced a dedicated webpage which includes FAQs and regular updates.

Readable research

Readable Research (www.readableresearch.com) is an initiative from our colleagues at the University of Sheffield. Clear simple summaries of Neuroscience research are written by students and then reviewed by people who have personal experience of MND. We are looking at contributing to this project with summaries written by Sussex students and reviewed by the local people connected to MND.

We want to compile a list of people who are interested in reading and providing feedback on the summaries that our students write. We expect that you will read a summary no longer than 2 pages once every six months at the most, depending on the number of students and reviewers that we have.If this is something that you would be interested with, please contact g.joilin@sussex.ac.uk to express interest.

Project 1

Identification of non-coding RNA biomarkers for disease prognosis and progression in Amyotrophic Lateral Sclerosis

PI: Majid Hafezparast

Researcher: Greig Joilin

Diagnosis of ALS/MND relies on clinical judgement and investigations to exclude other conditions, a process that may delay diagnosis and therefore treatment for many months. It is also difficult in the individuals with MND to predict the speed at which the disease will progress. Therefore, finding an indicator (biomarker) of disease in blood will decrease delay in diagnosis, improve understanding of progression, and, because some biomarkers are also related to causation, facilitate development of new treatments. We have been working on identifying a group of molecules called non-coding RNA (ncRNA) in the blood of people with ALS as potential biomarkers. We have identified seven ncRNAs that allow us to predict if a sample is from people with ALS or not. However, these ncRNAs do not reflect the speed at which the disease will progress, so we need to search for ncRNA biomarkers that change over time so that we can both predict and track disease progression. This will be done with the use of ALS samples collected over the course of the disease that have been enrolled into a large clinical trial and crucially we will use machine learning techniques to identify complex patterns of changes in dysregulated ncRNAs. This will allow us to predict the behaviour of ALS more accurately, to understand key differences between people with ALS, to aid in treatment development, and hence to improve outcomes for people affected by ALS.

This work is supported by the Motor Neurone Disease Association and the My Name'5 Doddie Association.

Joilin, G., Gray, E., Thompson, A. G., Bobeva, Y., Talbot, K., Weishaupt, J., Ludolph, A., Malaspina, A., Leigh, P. N., Newbury, S., Turner, M. R., & Hafezparast, M. (2020). Identification of a potential non-coding RNA biomarker signature for amyotrophic lateral sclerosis. Brain Communications, 2(1). Read more here >

Project 2

The Role of Microglia-released microRNA in ALS Pathology

PI: Majid Hafezparast

Researcher: Libby Moody

Neuroinflammation is recognised as an important event in the progression of disease in patients with amyotrophic lateral sclerosis (ALS). As part of this process, resident immune cells of the central nervous system, known as microglia, are activated to release a number of proteins and chemicals which modulate the function of neighbouring motor neurons but at high levels can damage these cells. Our recent data show that cultured microglia also release a group of molecules known as microRNAs (miRNAs) with differential expression in non-activated versus activated states. Importantly, there is increasing evidence that miRNAs released from microglia play an important role in cell-to-cell communication by modulating gene expression in adjacent cells. There are, however, significant gaps in our knowledge about the identities of microglia-derived miRNA and their impact on motor neurons in the context of ALS pathology. This project will utilise both wild-type and mutant mouse models of ALS to address these gaps by identifying the miRNAs expressed by activated and non-activated microglia and to determine which of these miRNAs are released into the space outside of these cells, what effect this may have on motor neurons, and whether this may underpin ALS.

This work is supported by the Ann Merriman Memorial Scholarship by the Motor Neurone Disease Association.

Christoforidou, E., Joilin, G., & Hafezparast, M. (2020). Potential of activated microglia as a source of dysregulated extracellular microRNAs contributing to neurodegeneration in amyotrophic lateral sclerosis. Journal of Neuroinflammation, 17, 135. Read more here >

Project 3

Understanding the effects of the Loa mutation in cytoplasmic dynein on motor neuron diseases

PI: Majid Hafezparast

Researcher: Conor McKiernan