May Spotlight on MS Research at CÚRAM: Dr Una FitzGerald for World MS Day

In Ireland, there are approximately 10,000 individuals living with multiple sclerosis (MS), the most common neurological disease to affect young adults in Ireland.

Dr Una FitzGerald, principal investigator of the Multiple Sclerosis Research Lab and an investigator at CÚRAM, leads a consortium of researchers across Europe to develop a novel device and treatments for multiple sclerosis (MS), a devastating neurological disease.

MS disease has two phases: an early ‘relapsing remitting’ phase, during which patients undergo impairment such as double vision or limb weakness, followed by symptom dissipation for a period; and ‘progressive MS’, which is degenerative and patients report much-reduced mobility, increased fatigue and cognitive challenges. These symptoms often impair quality of life significantly, and in some cases lead to an inability to continue in full-time employment, or work at all.

Compared to the early phase of MS, for which there are about 20 different drugs, there are very few treatment options (2 or 3), which are approved for treating the later progressive and degenerative phase. Moreover, these may be suitable for only subset of people with MS. This is why FitzGerald believes it is imperative to continue to do basic research, to understand why late-stage disease presents so many challenges, and to develop new treatment methods and medical devices to help improve quality of life for all people living with MS, or caring for individuals with MS.

What in your mind are the biggest advances made in MS research in recent years?

The research that probably had the most attention at media outlets, was one that provided the best proof so far, that Epstein Barr virus (EBV), the virus that causes glandular fever, can in some individuals, cause them to develop MS. An epidemiological study was done by Kjetil Bjornevik and colleagues in Harvard, on 10 million subjects who had been in the US military.  People who were found to have had a higher level of antibodies to EBV were 32 times more likely to go on to develop MS (see https://pubmed.ncbi.nlm.nih.gov/35025605/).  This is intriguing, since 85% of the general population have antibodies to EBV, but 85% don’t end up with MS. EBV has been a theme in MS research for decades, and this is the strongest evidence so far that it can, in some individuals, contribute in part to the development of MS. 

For researchers working at the bench, the advances in ‘omics’ technologies (transciptomics, proteomics, metabolomic, glycomics) are shedding new light on the biology underpinning MS disease course. For example, in 2018, researchers in Sweden Scotland and Australia, did RNA sequencing on samples of individual cells taken from post-mortem MS tissue and they proved that the demyelinated areas of the brain had many different sub-types of oligodendrocyte lineage cells, some of which seemed to be turning on genes normally associated with the immune response (https://pubmed.ncbi.nlm.nih.gov/30420755/). This is one example of research that shows that the biology underpinning MS pathology is much more complex than we imagined. A better understanding of this should help to identify novel therapeutic targets.

What are the big questions that are still outstanding?

Why do different people experience different forms of MS?

Is the categorisation of pwMS into different types useful?

How can medical devices be exploited to optimise drug delivering across the blood-brain barrier in late-stage MS, when the barrier between the brain and the rest of the body is particularly impermeable?

How quickly can we develop better lab-based models of MS, so that more effective treatments can be developed?

What home-monitoring medical devices could be useful in confirming that a person is about to have a relapse or that they are responding as predicted to a disease-modifying drug?

How important do you think it is for people with MS to be involved in your research?

Involving patients with MS in our research has been extremely valuable.  In preparation for an ongoing biomarker study, we asked for feedback from patients with MS on a draft application for ethical approval to carry out the proposed MS biomarker research project.  The idea is to use rapid assay technologies to identify molecules within different body fluids, particularly saliva, that could be linked to ongoing disease or to responses to disease-modifying drugs.  We believe that this could help to improve the clinical management of MS.

Once the research project was started, the same individuals helped us to improve the protocols used when study subjects came on-campus to donate samples. They also advised on how much time we should allow for individuals to travel to campus and to participate in our research.

Another important reason for involving patients with MS in our research, is that they help us to better understand what living with MS is like, which is highly motivating and inspiring when trying to come up with ideas for the next research topic.

What motivates you most in your work?

The desire to better understand the biology underpinning MS pathology and to use this knowledge to inform new ways of monitoring and mitigating MS. Training future MS research leaders is also imperative, which is why I’m delighted to be working with the students who work is highlighted in the videos below.

Hear about the research projects underway in the MS Research Group;

Bianca Castelli- https://vimeo.com/951549524

Daniela Costa- https://vimeo.com/951549933

Shima Shapoori- https://vimeo.com/951550223

Paola Serrano- https://vimeo.com/951550447

Malgorzata Dabrowska- https://vimeo.com/951550674