The role of dopamine in Huntington’s disease
In the Huntington’s disease (HD) brain, the pathology affects the dopaminergic system Interestingly, the most commonly used treatment for the motor symptoms of HD blocks dopamine receptors suggesting a decrease in dopamine signaling may be beneficial in this disease. However, to date, very little attention has been paid on the effect of these drugs in animal models of HD. This research aims to investigate the dopaminergic system in animal models of HD.
The role of the immune system in Parkinson’s disease and its associated dementia
Parkinson’s disease progresses at different speeds in different individuals, with some individuals having a rapid disease course and developing memory problems and a dementia within a few years of diagnosis, and others having a more benign course with relatively little disability for many years. Dementia in PD occurs when the pathological changes (including the deposits of alpha synuclein) spread from the deep movement centres of the brain out to the outer cortex, but the factors driving the rate of this progression of pathology are not well understood. The immune system may play a critical role, and would be an attractive target for disease modifying therapy. Such therapy is much needed given the devastating impact of dementia on the patient and their family, and the lack of effective therapies for this aspect of the disease currently available.
This programme of work is supported by generous funding from the following charities and organisations: Academy of Medical Sciences, Rosetrees Trust, Addenbrooke’s Charitable Trust, Wellcome Trust, Stevenage Biosciences Catalyst.
Gaucher’s disease and Parkinson’s disease
This work centres on a recently described genetic predisposition to developing Parkinson’s disease that relates to the gene causing Gauchers disease. The work is based in the lab on creating neurons from skin cells collected from skin biopsies. These neuronal models are a unique research tool as they represent person specific cells. The aim is to use these neurons to model the neurons affected in Parkinson’s disease. The technique is very new so we are currently optimising the experiments and for this we are working with Dr. Malin Parmar’s group from Lund University who are experts in this technique.
This work is supported by the Rosetrees Trust and ARUK.
Using stem cell-based approaches to model Parkinson’s disease dementia in human brain cells
Human induced pluripotent stem cells (iPSCs) can be generated from adult cells such as skin cells. Using the right culture conditions, these iPSCs can then be differentiated into functional nerve cells.
In a collaborative project with the Livesey group we use cerebral cortex neurons to model neurodegeneration and dementia associated with Parkinson’s disease in a human-based cell culture system. This stem cell-based approach allows us to study aspects of disease initiation and progression in human brain cells as it was not feasible previously. We are particular interested in the role of the protein alpha-synuclein that forms the abnormal aggregates that are a hallmark of PD.
Disease modelling
We are trying to better model the clinical progression of Huntington’s disease (HD). By working with engineers, we have shown that the trajectory of HD progression can be modelled and predicted for individual patients. With data from clinical assessments over the past 2 years, it is possible to predict how disease would progress over the next 2 years with a 90% accuracy. The aim is to minimise the need to use placebo control in clinical trials.We are now working to refine and improve the model and prediction accuracy. This work is mainly supported by the Rosetrees/Butterfield Trust.
Cell transplantation
We are working to improve the outcome of cell transplantation therapy in Parkinson’s disease (PD). 90% of the grafted cells are lost in the first two weeks post-transplantation due to the hostile environment in the adult central nervous system. We are now seeking to develop better ways to protect these cells by grafting them with supporting scaffoldsThis work is mainly supported by the UK Regenerative Medicine Platform (UKRMP).
