Research in the Multiple Sclerosis Labs, Bristol

The Multiple Sclerosis and Stem Cell Research Group is part of the University of Bristol Institute of Clinical Neuroscience and is based at the Glial Cell Biology Laboratories at Frenchay Hospital. Our activities centre, in particular, on the underlying cell biology of multiple sclerosis. The development and implementation of myelin repair treatments and understanding mechanisms of neurodegeneration. Research focuses on developing new therapeutic strategies for multiple sclerosis. Oligodendrocyte progenitors are the cells responsible for most spontaneous remyelination. Using post-mortem specimens we are examining the role of oligodendrocyte progenitors in normal brain and MS lesions. Unfortunately, while oligodendrocyte progenitors can be isolated from the adult human brain, and can undergo limited proliferation in vitro, the numbers of these cells are limited and their migration through normal brain is considerably impeded. Stem cells, with their significant replicative potential, provide a possible solution to this problem. We are working on the identification of signals which direct the differentiation of neural stem cells along the oligodendrocyte lineage with a view to developing this as a potential transplantation strategy for MS. An alternative source of autologous stem cells for transplantion is the bone marrow and we are also investigating the potential of bone marrow-derived stem cells to differentiate along the neuroectodermal lineage. Research is also being undertaken to explore the cause of axon loss in the disease. We are taking forward several observations on axon dysfunction and translating these into the development of new therapies for chronic disease progression. We are also interested in the immunological aspects of the disease. In collaboration with David Wraith, from the University of Bristol Department of Pathology and Microbiology, we are investigating ways to manipulate the immune system in the hope that new treatments can be developed. Clinical research within the lab focuses on the causes of disability in chronic MS and a study of Primary Progressive MS (PPMS).

We are interested in stem cells as a treatment for multiple sclerosis

We are exploring the reasons for nerve fibre loss in multiple sclerosis

Dr. Elizabeth Gray has been awarded a prestigious Junior Research Fellowship from the MS Society. Her project is: Neuroprotection in progressive multiple sclerosis: the role of the peroxisome Nerve cell damage is recognized to be an important contributor to disability in multiple sclerosis. It is thought that nerve cell damage may occur both during relapses of the disease, but also as a slow degenerative process once patients have had the disease for some time. This latter phase is known as disease progression and during this phase there is a clear quantitative relationship between nerve cell damage and disability. To date, no therapy has been shown to impact significantly on the progressive phase of multiple sclerosis, probably reflecting the inability of current treatments to protect nerve cells specifically. We aim to determine mechanisms by which nerve cells may be protected. Specifically we are interested in the role of drugs which may improve the function of a nerve cell component called the peroxisome. Such drugs are is regular use for other conditions, such as diabetes, but there is evidence that they may directly protect neurons. We have already confirmed peroxisomes to be present in cultured nerve cells and post-mortem tissue from MS patients. We can promote the survival of damaged nerve cells by exposure to drugs that increase the function of peroxisomes. Aims of project This project will use a number of methods and employ models of multiple sclerosis as well as tissue derived from patients who have suffered from the disease. Specifically we aim to investigate: (a) the amount of peroxisomal activity in brain tissue donated to the multiple sclerosis tissue bank (b) the distribution and function of peroxisomes in cultured nerve cells (c) the effect of peroxisomal activators on nerve cell survival and the mechanisms by which this occurs (d) the consequences of increasing endogenous peroxisomal function in models of multiple sclerosis. We hope that these studies will lay the foundations for trials, in due course, of peroxisomal activators in progressive multiple sclerosis.

 

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