Authors: Alice Weatherston
Neurology Central Expert Panelist, Professor Monica Busse (Cardiff University, UK), is a physiotherapist with an established interest in exercise and physical activity for individuals with chronic health conditions, with a particular focus on neurodegenerative diseases.
We found out more about her current research focuses and involvement in a range of multicenter studies evaluating the potentially functional and disease-modifying effects of physical activity in Huntington’s disease. This work includes investigating the role of exercise in facilitating graft integration in cell transplantation, an exciting novel intervention.
What initially sparked your interest in neurology?
I was involved in disability sports in school and my first job was as a physiotherapist working in spinal cord injury rehabilitation in South Africa. My interest in the field has developed since that time, through working in inspiring facilities in the US and for the last 16 years, the UK. It is the potential and the challenge to really make a difference to people with neurological diseases that keeps me interested.
At present, what are the main focuses for research in your team?
Our current focus is on preparing for impending cell transplantation in Huntington’s disease (HD). Given what we already know in animal models of transplantation, it is highly likely that activity-based interventions are going to be important in facilitating graft integration in human populations. Of interest, is that no existing cell transplantation trials (in HD or in Parkinson’s disease) have explicitly considered the role of training in graft integration as part of the process. We are now developing novel sensitive assessments of function and studying optimal methods for physical and cognitive activity pre- and post-surgery through REPAIR-HD and funding from Health and Care Research Wales Brain Repair and Intracranial Neurotherapeutics Unit (BRAIN).
You have played a key role in a variety of trials on the effects of exercise on Huntington’s disease, can you give us an overview of these?
Our work studying the effects of exercise in HD started in 2007. At this point, we realized that there was in fact very little evidence in support of physical interventions for this complex condition. Developing these approaches was for us very important, as it was fairly well established at this point that both environmental enrichment and training was a factor in delaying onset of symptoms in animal models of HD and as previously mentioned was also crucial to graft integration in cell transplantation in animal models.
The challenge for us however was that we did not know enough about mobility impairments in HD or indeed about what kinds of exercise interventions would be beneficial. We took a staged approach, guided by the Medical Research Council Framework for Developing and Evaluating Complex Interventions. We conducted the first ever randomized controlled trial of exercise in HD and have gone on to conduct a series of multicenter randomized controlled trials that have provided incremental evidence that people with HD can achieve fitness and functional benefit from specific exercise training.
In addition, we were the first research unit to demonstrate quantifiable evidence of muscle weakness in HD in comparison to age-matched healthy controls and to highlight the increased risk of falls in this population. We also led on research to validate and optimize appropriate performance-based functional outcome measures in a multicenter, international observational study (UK, Netherlands, USA and Portugal) for use in HD.
We have recently completed a multicenter trial of a more intensive multimodal exercise intervention (ExeRT-HD) where we reported significant increases in fitness along with significant improvement in motor function in those who exercised.
One of our challenges however has been that once our trials end, our participants tell us that they don’t continue to exercise. In order to address this, we developed an intervention (ENGAGE-HD) to enhance exercise uptake and continued engagement.
I feel very strongly that active involvement from patients and their families leads to research and the development of interventions that are more relevant, more reliable and more likely to be used to improve the health and wellbeing of people living with HD. Through BRAIN Involve, our public and patient involvement group, we continue to encourage and support people to use their experiences to help inform and develop our research activities. We have also worked closely with physiotherapy colleagues from the European Huntington’s Disease Network (EHDN) and to share our research findings but also to make sure that our interventions are culturally relevant and applicable to the wider population.
Why is lifestyle/exercise so important for Huntington’s disease patients?
In addition to what we already know, from animal model work and our work in individuals with HD, about the functional and potentially disease-modifying effects of lifestyle and exercise, participation in regular physical activity may provide people with HD with a sense of self-confidence, wellbeing and control over one’s life in the context of a long-lasting degenerative disease currently without a cure.
Through our focus group work with people with HD, family members and carers we have observed that participation in regular activities may provide opportunities for people with HD to extend their social network, reduce the isolation that people with HD often experience and potentially reduce burden on family members. Indeed, in addition to the potential physical and functional benefits, there are potential gains for maintaining or improving quality of life over the long-term.
How do you hope this research will influence the management and treatment of Huntington’s disease?
Ongoing health and social care is required to support the challenging and changing needs of those with HD. It is vital that every opportunity is available for people with HD to maintain adequate quality of life for as long as possible. One way of achieving this is through participation in physical activity.
Maintaining fitness and physical function from the point of diagnosis is vital for maintaining quality of life for people with HD and is especially important given the duration of the disease and known burden on the individual, their personal support network and the healthcare services.
Ongoing efforts to define physiotherapy interventions, validate outcome measures and conduct robust evaluations of targeted physiotherapy led interventions have shown that people with HD can achieve fitness and measurable functional benefit from specific exercise training. Indeed community and home-based exercise interventions have been shown to be enjoyable and acceptable for people with HD. Sustained engagement in meaningful activities is vital in HD where quality of life both in terms of physical and psychosocial wellbeing are severely affected.
To sustain an active lifestyle, support and adaptation are important, so that when changes occur, people are equipped with strategies and have appropriate support to deal positively with their changing abilities in a way that enables them to continue to be active for as long as possible.
Unfortunately experiences of people with HD across the UK, in trying to access support and information to be more active, suggests that there is inconsistency of provision for physical activity within the healthcare system and local council leisure service. Although the consequences of physical inactivity in terms of cost in HD have not been explored we do know that average healthcare cost across all stages of disease is around £21,605 per year. This equates to £195 million per year in the UK. As would be expected with a degenerative condition, quality of life declines and mean costs increase with disease severity. We hope that we see greater investment in care and support, including physiotherapy and physical activity for people in the earlier stages of HD to keep them functioning as well as possible for as long as possible.
You are also part of the Repair-HD trial aiming to expand our understanding of stem cell treatments for Huntington’s disease, do you think that this will be a significant area for treatment of the disease in the future?
Cardiff leads the international consortium REPAIR-HD, which is developing all the elements required for first-in-man trials of using pluripotent stem cell derived donor cells. Indeed, over three decades, Cardiff researchers have been at the international forefront of developing regenerative medicine approaches to treating neurodegenerative disorders, notably Huntington’s disease (HD) where transplantation is the only therapy to date where proof of concept for cognitive improvement exists.
This research is underpinned by a wealth of in vitro and whole animal studies demonstrating the efficacy of primary fetal and next-generation stem cell products. Cardiff researchers led the first UK trial of primary fetal cell transplants in HD. This work is continuing through the BRAIN unit with the second cohort of transplants planned for 2017. As a physiotherapist researcher, I feel incredibly fortunate to have the opportunity to work with such cutting edge research and I am confident that this is going to lead to exciting treatment options for the future.
What do you think will be the next big breakthrough for the treatment of Huntington’s disease?
Undoubtedly there is great interest in gene silencing approaches for the treatment of HD (see), however I remain very optimistic about the incredible opportunities to be afforded by regenerative medicine approaches especially when combined with activity-based exercise and cognitive training protocol (or indeed gene silencing).
Recent related study from Monica Busse: Quinn, L et al. Development and delivery of a physical activity intervention for people with Huntington Disease. Journal of Neurologic Physical Therapy. 71–80, 40(2) (2016).
The opinions expressed in this interview are those of the interviewee and do not necessarily reflect those of Neurology Central or Future Science Group.