Fellowships are competitively obtained prestigious research awards which allow fellows to establish their own independent research careers.
Dr Tom Massey
Funders: MRC Post-doctoral Clinical Research Training Fellowship and Patrick Berthoud Charitable Trust Fellowship
Huntington's Disease (HD) is caused by expansion of a ‘CAG’ repeat in the DNA of the Huntington’s disease gene: the greater the number of repeats, the earlier the disease starts. Exactly how this leads to specific nerve damage and loss in the brain is unknown.
One idea is that the DNA repair systems that normally protect our genes from mutation, and our cells from cancer, can sometimes act incorrectly on CAG repeats and cause them to expand in length. Recent genetic studies have reinforced this view and identified elements of the DNA repair machinery in cells that may trigger expansion.
We will test these repair proteins in model laboratory systems of cells in which we can trigger CAG repeat expansion. If we can identify DNA repair components (or pathways) that affect CAG repeat size, these could represent novel drug targets. In theory, selectively blocking pathways that trigger repeat expansion could delay (or even prevent) the onset of HD and so there is potential for this work to be translated into new therapies. Any treatment that affects the onset or course of HD would represent a major step forward in therapy.
WCAT Fellow, Division of Psychological Medicine and Clinical Neurosciences
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Dr Jessica Steventon
Funder: The Waterloo Foundation
My fellowship is focused on better understanding the neural mechanisms underlying observed beneficial effects of exercise. The long-range objective is to gain insight into how exercise can be optimally prescribed as a therapeutic intervention to people with Huntington’s disease (HD). My research aims to explore the therapeutic potential of exercise to reduce the severity of symptoms and slow the rate of symptom and pathology progression.
Exercise has been found to be associated with a range a health benefits, and can reduce the severity of symptoms in a number of neurodegenerative and neurodevelopment disorders, including HD. However, it is not clear why these beneficial effects occur, how long-lasting they are, and the dose and type of exercise required.
My research approach is to use an array of magnetic resonance imaging (MRI) techniques to characterise exercise-induced cerebral vasculature changes. Towards this end, I am working collaboratively with researchers in Cardiff Huntington’s Disease Physiotherapy group and working closely with people with HD and their families, conducting physiological and exercise tests and assessing the relationship with functional brain measures.
We wish to examine whether the cerebrovascular response is the same in healthy people and people with HD. The outcome of this work will potentially inform how exercise is prescribed in people living with HD.
Dr Emma Yhnell
Funder: Health and Care Research Wales
Computerised cognitive training interventions that focus on improving executive function present a potentially exciting non-pharmacological treatment option.
Novel work conducted in mouse models of HD, has demonstrated that cognitive training, administered from an early stage in the disease, can improve motor performance at an older age, even in the absence of further training in the intervening time. This demonstrates in an animal model of HD that cognitive training can improve HD disease symptoms. Improvements associated with executive function training have also been reported in a clinical setting in a variety of neurodegenerative diseases such as Parkinson’s disease (PD) and Alzheimer’s disease (AD).
Therefore, this study is a feasibility study which uses HAPPYneuron software and aims to establish proof of principle for using computerised cognitive training in people with HD.
We will also study brain structure and function, using MRI scanning techniques with colleagues in the Cardiff University Brain Research Imaging Centre (CUBRIC) through funding from the Jacque and Gloria Gossweiler Foundation. The South East Wales Trials Unit, Centre for Trials Research are providing advisory support throughout the Fellowship award.