#LoveIrishResearch BLOG: Highlighting National Arthritis Week

Image: blood vessels in the inflamed RA synovium (top), and MRI/PET hybrid imaging of the RA joint (below). 

To highlight National Arthritis Week and celebrate our October #LoveIrishResearch theme, “Research for a Healthy Life,” Postgraduate Scholars Megan Hanlon and Sean McKenna have written to tell us about their research into Rheumatoid Arthritis.

Megan Hanlon is a postgraduate scholar in the Department of Molecular Rheumatology at Trinity College Dublin’s School of Medicine. Her thesis looks at the resolution of inflammation through metabolic reprogramming of synovial macrophages in RA.

Arthritis is a leading cause of disability that affects up to 15% of the population and is the most common cause of pain in Irish society, including children. 2% suffer from inflammatory arthritis (IA) such as rheumatoid arthritis (RA) and psoriatic arthritis (PsA). IA causes joint damage and disability and is associated with co-morbidities such as cardiovascular disease, malignancy and metabolic disorders.  Targeted therapies have improved the outcome, however they are limited by inefficacy or sub-optimal responses in patients, while others suffer from adverse events. The costs of RA to the individual, society and the healthcare system are high, therefore new treatment strategies are needed.

I am performing my research in the Department of Molecular Rheumatology (TBSI, TCD), focusing on understanding the underlying mechanisms that drive disease pathogenesis in Rheumatic diseases. Our body fights infection in a number of ways, with activation of immune cells being a key mechanism. However, if uncontrolled, this activation can contribute to the development of auto-immune diseases such as RA.  In the joints of RA patients, many new blood vessels grow, allowing immune cells from the blood to invade into the synovial membrane, leading to low oxygen levels (hypoxia). This is associated with increased joint inflammation and destruction of cartilage and bone. This hypoxic environment leads to a dramatic change in the metabolic activity of the cells at the site of inflammation (synovium), due to their increased demand for energy. Thus synovial cells adapt by changing their metabolic profile to one that can more rapidly produce energy, which allows them to maintain cell activation and function. So, if we can develop therapies that can switch synovial cells to a normal metabolic profile, we may be able to suppress inflammation.

In this project, I will focus on a specific synovial cell sub-type, the macrophage, which is one of the key cell types in the inflamed joint and has previously been shown to be associated with increased disease activity and response to therapy.  There is growing evidence that a change in the metabolic profile of the synovium in RA induces a pro-inflammatory macrophage phenotype, which further increases the chances of disease pathogenesis. The aim of my research is therefore to elucidate the metabolic profile of macrophages, and investigate how synovial-macrophage metabolism can be therapeutically manipulated to either promote or inhibit inflammation.

During my research project, funded by the Irish Research Council’s Government of Ireland Postgraduate Scholarship, I will have a close working relationship with my supervisor Prof. Ursula Fearon as well as the other members of our team including PhD students, postdoctoral scientists  and research assistants. However, this will also be a multidisciplinary effort involving basic scientists, clinicians and importantly the patients, without whom we could not perform this research. We have developed a number of models using human tissue from patient with inflammatory arthritis, which closely reflects the living joint environment thus allowing us to have a translational bench-to-bedside approach, and the potential to have real impact on the lives of RA patients. The findings of our research will assist in the identification of new disease markers, drug targets, and drug candidates for the treatment of patients with RA, which is extremely exciting.  

Sean McKenna is a postgraduate scholar in the Department of Clinical Therapies at the University of Limerick. His research explores the effects of exercise on sleep, depression and anxiety in people who have Rheumatoid Arthritis.

I graduated as a Chartered Physiotherapist from the University of Limerick in 2014, where I was a mature student. The opportunity came up to continue my interest in exercise and rheumatoid arthritis, and I commenced my structured PhD studies at the Department of Clinical Therapies, at the University of Limerick, under the guidance of Dr. Norelee Kennedy. Rheumatoid arthritis (RA) is an autoimmune disease, which causes chronic inflammation of the joints and injury to the organs of the body. It is the most common type of inflammatory arthritis, affecting between 0.5% and 1.5% of the general population, with women being affected more than men.

Physiotherapy is frequently used as an intervention for people with RA and, in recent years, research on its effectiveness has grown with regards to physical outcomes measured. There is a growing body of literature revealing that regular exercise may help sleep, depression and/or anxiety and lead to anti-inflammatory effects in chronic diseases, but there has been little research so far into how the same factors might help in the treatment of RA. It is therefore important to look at people who have RA in the larger social context, the practicalities of delivering exercise and the psychological impact on those involved. This is precisely what my research aims to do.

In general, getting fewer than five hours sleep per day has been associated with cardiovascular problems, diabetes and obesity and can also be linked to depression, anxiety and poor productivity. While exercise and drug therapy constitute the major cornerstone for RA management, showing benefits from physical outcome measures such as fatigue, muscle strength, aerobic capacity and pain, there is limited evidence on exercise’s effects in improving sleep, better mental health and indeed its anti-inflammatory effects. If demonstrated, this link could act as an adjuvant tool in improving not only overall symptoms but also the disease course in RA.

Irish health research priorities include the study of chronic conditions, cost-effectiveness and practice education (according to the Identification of Research Priorities for Therapy Professions in Ireland, 2010). In line with this, my project aims to understand both the physical and psychological effects of exercise in addition to the anti-inflammatory properties of exercise in people with RA. The ability to measure such changes may open up the possibility of designing new and objective approaches to defining the benefits of physical activity and exercise in this population.

The social determinants of health are a range of factors that impact upon health and wellbeing for all, including those with a chronic condition. International evidence shows that to effect sustainable improvements in health and wellbeing, a whole system approach is needed, involving government and society. Therefore, the involvement of all stakeholders from the start ensures the exercise intervention is acceptable and feasible, and ultimately reduces any health inequalities for people who have RA. My research project will be the first of its kind to show how a specific intensity exercise intervention may help improve sleep and mental health outcomes, in addition to being cognisant of the importance of the economics of health.