MS Projects

Multiple sclerosis (MS) is a severely debilitating disease that damages myelin, a protective sheath around nerves, in the central nervous system. Myelin allows electrical impulses to transmit quickly along nerve cells, and its regeneration has the potential to be restorative for
patients with MS. It was recently discovered that a particular type of immune cell, regulatory T (Treg) cells, play an important role in myelin regeneration. 

Therefore, a deep understanding of how Tregs are induced from normal immune cells could lead to the development of novel therapies. Emerging evidence suggests that Treg induction depends on how immune cells respond to physical forces in the body, although the driving factors are unclear. We are investigating how these physical forces are sensed by immune cells in order
to drive Treg induction, and whether Tregs can subsequently maintain their function for immunotherapy applications. 

To carry out this work, we will combine advanced biomedical engineering simulation with cell-based experiments. Our investigation will provide a foundation for developing new biomaterials and treatments for MS immunotherapy.

PI website: mechanomodel.ie
PIs: Dr Eoin McEvoy (University of Galway)
Prof Denise Fitzgerald (QUB)
Postdocs: Dr Muhamman Qasim (University of Galway)

Dr Jessica White (QUB)
Dr Rosana Panalva (QUB)

Through the use of a microfluidic device which models the surface of the brain, we are developing a method to assess the factors which may influence their formation and their harmfulness to other cells in the brain. This device will utilise technologies to allow us to miniaturise the model enabling it to reduce cost and increase throughput.

Ultimately the development of this device will allow for a more detailed study of these pathological features and their contribution to disease course. Multiple Sclerosis (MS) is an auto-immune
disease of the central nervous system. Its pathogenesis is complex initially resulting in intermittent, and subsequently, often progressive neurological defects. Modelling of MS is a
great challenge and there is not an experimental model in existence which can replicate the range of the clinical, pathological, or immunological features of the disease. Advanced in vitro models can replicate specific characteristics or features of the disease, hence creating a method to determine the exact role of these factors.
An auto-immune disease in origin this project aims to recreate an immunological feature found in up to 40% of patients with progressive MS. The feature consists of a number of cell
types and are referred to as lymphoid-like follicles (LLfs). Through the use of a microfluidic device which models the surface of the brain, we are developing a method to assess the factors which may influence their formation and their harmfulness to other cells in the brain. This device will utilise technologies to allow us to miniaturise the model enabling it to reduce cost and increase throughput. Ultimately the development of this device will allow
for a more detailed study of these pathological features and their contribution to disease course.

– Patrick C Hurley
Doctoral Candidate / University of Galway

According to the Multiple Sclerosis International Federation (MSIF), 2.8 million people worldwide have been diagnosed with multiple sclerosis (MS), making it the most common immunological
disease of the brain. However, diagnosis can be a lengthy process, as the necessary diagnostic tests, such as MRI scans and lumbar punctures, are not always conclusive, and can also be expensive and
invasive. Furthermore, specialist knowledge from consultant neurologists is required and referral from your GP can take a long time.
Besides delays in getting an initial MS diagnosis, all these problems also impact the all-important monitoring of disease progression, which helps inform clinicians on treatment plans and care packages needed.
Doctors need to know how people are responding to treatment or what sort ofsymptoms they are developing. Moreover, lack of access to consultant care and the necessary hospital tests can have a real impact on someone’s quality of life. With this project, we hope to tackle, if only in part, some of these challenges. The initial hypothesis is that some of the biomarkers that are already correlated specifically to MS can be found in the body fluids that are easily accessible (e.g., saliva, nasal secretions, tears, and blood) samples. These markers, which can be taken in a non-invasive manner and without the need for a specialist, can be useful for MS diagnosis and monitoring. “Ultimately, using innovative technology, our team’s end goal is to develop a rapid test that will improve the clinical management and lives of people with MS”.
This project is led by Dr Una FitzGerald and Dr Jill McMahon at the University of Galway and is being carried out in collaboration with Dr Marwa Elamin and Dr Tim Counihan, Consultant Neurologists at University Hospital Galway. The research is being carried out by PhD candidates Shima Shapoori and Bianca Castelli.

Short videos explaining Shima’s and Bianca’s research in more detail are below.

MS research group calls for volunteers to improve diagnosis and monitoring.

My primary research interest is in the molecular and cellular basis of brain function in Multiple sclerosis (MS), Alzheimer’s disease (AD), and Huntington’s disease (HD). My lab is characterising the mechanism and role of oestrogen, GABA and glutamate signalling in these neurodegenerative diseases using interdisciplinary approaches, combining molecular, physiological and anatomical techniques. We study the molecular components, and the molecular and cellular architecture of these multifunctional signalling systems and aim to elucidate their physiological role in the ageing and diseased brain. Our goal is the identification of new drug targets, drug testing, and development of imaging tools and brain stimulation technology.

Areas of Expertise: Neuropharmacology, Human neurodegenerative diseases, Gamma-aminobutyric acid (GABA) and Glutamate signalling, Oestrogen signalling, Neurotrophin signalling, Neuroprotection, Neuroinflammation, Inflammasome.

Techniques
MS post-mortem tissue analysis
In vitro and in vivo animal models
In vitro and in vivo calcium imaging, electrophysiology and optogenetics
Behavioural testing
Molecular biology and genetics

This research is being supervised by Dr Andrea Kwakowsky, Lecturer, Pharmcology and Therapeutics.
For further details, see https://www.universityofgalway.ie/medicine-nursing-and-health-sciences/medicine/staff/staffprofiles/andreakwakowsky/.

 

Currently, one of the big limitations to treating progressive MS is that many drugs cannot get from the blood stream into the brain because of what is known as the blood brain barrier (BBB). The BBB exists only in blood vessels in brain tissue, and it prevents damaging or poisonous substances reaching brain cells from the circulation. The PMSMatTrain project aims to develop new technology that allows controlled delivery of therapeutic molecules directly from a minimally invasive device on the skull to the outer layer of the brain (known as the cortex), effectively by-passing the BBB.  

By using materials in the device that mimic those occurring in nature (biomaterials), the aim is to deliver a cocktail of drugs, which is tailored specifically to treat the later progressive stages of MS. This cocktail would be comprised of anti-inflammatory agents and molecules which both protect brain cells and promote tissue repair, and it is hoped they can be released to the brain at different rates as they are needed. Known as multiphasic drug delivery, this is made possible by development of specialised “tuneable” biomaterials that are customised to the specific properties of the therapeutics being used.

The project involves production of novel customised biomaterials, device development and manufacture, drug and device testing in cutting-edge models of MS pathology, as well as computer modelling of drug release and dispersal in the tissue. Coordinated by Dr Úna FitzGerald, the project is funded by the EU, and supports 15 early-stage researchers in 8 European countries.

Please visit the PMSMatTrain website for further details https://pmsmattrain.eu/.

The researchers in the University of Galway who are part of this consortium are Daniela Costa, Małgorzata Dąbrowska, Jack Hampson, Yagmur Bozkurt and Mansoor Al-Waeel. Short videos explaining the research carried out by Daniela, Małgorzata and Jack,  accessible at the links below.

 

Dr Claire McCoy at RCSI, Dr Una Fitzgerald at NUIG and Dr Yvonne Dombrowksi at QUB are scheduled to begin a project on 1 May 2021, entitled “MiRNAs as therapeutics for neurorepair in Multiple Sclerosis”. The work will be led by María Muñoz San Martín who was awarded a Marie Skłodowska-Curie Actions Individual Fellowship in the 2020 call. This heralds the first ‘offical joint project’ under the remit of the AIMS Research Network and promises to bring together lead scientists in Ireland to address a fundamental research question in the MS field.

The main aim of the project is to identify microRNAs involved in the damage and endogenous repair associated with MS by combining human miRNA data with robust experimental models. In addition, the modulation of selected miRNA expression will be studied as a therapeutic tool in conjunction with novel bioscaffolds to promote neurorepair in MS.

There are a range of medicines that are available to treat multiple sclerosis (MS). The difficulty for the MS team is how to select the right drug for the right patient. At the moment there are no tests for an individual to see if they will respond to a drug or not. The choice is made based on the results of a trial with a large group of people.

The problem is that these group level results do not always capture the unique characteristics of that individual. Arising from this problem, this study aims to explore whether we can predict response to treatment in MS. This would help doctors and nurses in the MS clinic so that a medicine offered to each person would be based on their individual measures.

To do this we will ask a group of people with newly diagnosed MS to come in for testing. This will involve some questions about medical history and an examination. The team will also do three tests: a blood test, an eye test and an MRI scan.

These three tests are to measure the degree of inflammation at baseline before the full effect of treatment is known. We have chosen to measure inflammation as it both causes damage in MS and is the target of treatment.

At a one-year time point the same people will be asked to a return visit where the team will record whether there was a response to treatment or not in each individual.

The overall aim of the study will then be to establish if any of the baseline tests of inflammation were able to predict response to treatment. We hope that this will lead to an improvement in care for people with MS.

 

Please visit Dr Hugh Kearney’s profile page for more details.

Our research is currently focused on the conduct and delivery of a clinical randomised controlled trial of the COB-MS.

Cognitive problems, like inability to hold a conversation or remembering where you left your keys, are common symptoms experienced by people living with multiple sclerosis (MS). The effect can be wide reaching, from struggling to remain in the workplace, to self-care. The healthcare professional who usually treats the patient is the occupational therapist (OT). There has been no occupational therapy treatment developed and tested for this devastating symptom until the development of COB-MS (a therapy to help with cognitive issues associated with MS, taught by OT).

We have already tested this method in a feasibility study. OT’s and people living with MS were positive about COB-MS. Based on this, we want to know the clinical effect of the therapy and if the cost of delivering the therapy is practical, compared to if the patient didn’t change their normal treatment (the control group). This study will have three groups – online, in-person, and a control group. The feasibility study was online, because of the COVID-19 pandemic, and now we want to check online and in-person delivery of COB-MS.

We focus on critical priorities in MS recovery, occupational therapy and trial methodology. By including the MS community, experts in trial methodology, health economics, statistics, and health service research, we hope to improve the quality of life of people with MS nationally and internationally. Potentially helping with distressing cognitive challenges and reducing the cost to society.

 

Please visit Dr Sinéad Hynes’ profile page for more details.