Dr Emma Lane - BSc PhD
Member of the School's Pharmacology & Physiology Research Group
Parkinson’s disease and Huntington’s disease are neurodegenerative movement disorders in which there is a progressive loss of specific groups of neurons in the basal ganglia circuitry. The Brain Repair Group is a 30-strong multi-disciplinary team of biomedical and clinical scientists, students and support staff, under the co-direction of 3 PI's, Dr Emma Lane, and Professors Stephen Dunnett and Anne Rosser (in the School of Bioscience).
Parkinson’s disease is a largely sporadic disorder which affects around 120 000 people in the UK. It is most commonly described as a motor disorder, with the cardinal features of resting tremor, rigidity, bradykinesia and postural instability. The main pathology is the loss of the melanised dopaminergic neurons of the nigrostriatal pathway and the development of protein accumulations immunopositive for the protein a-synuclein. Many of the motor symptoms of Parkinson’s disease can be well controlled in the early stages with dopaminergic drugs therapies, however as the disease develop, the main treatment for Parkinson’s disease, L-dopa, causes the development of abnormal involuntary movements. These can be severely debilitating and there are currently few pharmaceutical interventions to prevent or ameliorate them. Understanding the features that predispose for the development of L-dopa induced dyskinesia may increase our ability to identify patients at greater risk and avoid or minimise them with careful management of medication. Furthermore, the effects of L-dopa may go beyond motor activation and I am interested in the possible effects of long-term L-dopa administration on motor learning and habit formation using in vivo models of PD and dyskinesia.
Not only do dyskinesia develop, but medication become less effective at treating the motor symptoms of PD as the disease progresses. Transplantation of foetal tissue into the striatum can replace the lost dopaminergicinnervation and can produce remarkable improvements in motor function. However, clinical trials have identified issues that need to be carefully considered before further clinical trial of embryonic tissue or cells from alternative sources (ie stem cells) can be attempted, including reliability and reproducibility of positive results, access to sources of embryonic tissue and alternative cell types and most notably the issue of transplantation-induced side effects. Three clinical trials of transplantation with embryonic tissue have now reported the development of dyskinesia in transplanted patients unrelated to their medication, to the extent that several have required further surgical interventions to ameliorate their symptoms. The main focus of my research over the last 5 years has been in determining mechanisms and contributing risk factors for the development of post-transplantation dyskinesia in order that transplantation can proceed unhindered into the next phase of clinical trials soon to be established with the Transeuro EU FP7 award recently awarded to a consortium of several EU teams, one of which is based at Cardiff University.
Huntington’s disease is a genetic disorder affecting around 7000 people in the UK. An elongated stretch of CAG repeats on the gene encoding the protein Huntingtin is responsible for progressive motor, cognitive and psychiatric symptoms. One of the motor symptoms can be choreiform abnormal involuntary movements often occurring in the earlier stages of disease. Our early studies are looking at how these maybe represented in animal models of Huntington’s disease to increase understanding and treatment strategies targeted towards this aspect of the disease.
Wellcome Trust Biomedical Vacation Scholarship application for summer student James Davidson
Scanning changes in functional brain activity associated with dyskinesia in parkinsonian rats. Parkinson’s Disease Society Innovations grant, £15 000 (PI with Stephen Paisey and Stephen Dunnett)
Wellcome Trust Value In People Award.
Does the storage of embryonic tissue prior to transplantation affect immune responses to the graft and the development of graft induceddyskinesias?Parkinsonfonden, 100,000 SEK (PI)
Understanding and eliminating the dyskinetic effects of nigral grafts. (Co-PI with Stephen Dunnett and ChristelleMonville,)
Pharmacological investigation into amphetamine induced dyskinesiaParkinsonfonden, 100,000 SEK (PI)