The UK Multiple Sclerosis Tissue Bank
Welcome Introduction How to register as a tissue donor Raising awareness of all those affected by MS Donation of Tissue Requesting tissue for research on multiple sclerosis Promoting the Tissue Bank in the research community The Bank Statement Issue One Issue Two Issue Three Articles MS Matters Insight - Banking on the future MS Frontiers - A very special bank MS Frontiers - Making a very special contribution Links: Department of Cellular and Molecular Neuroscience Department of Neuropathology Multiple Sclerosis Society of Great Britain and Northern Ireland International Federation of Multiple Sclerosis Societies E-mail: ukmstissuebank@imperial.ac.uk	the Bank Statement Issue Two (The Bank Statement is also available as a PDF document.) 2. Earliest changes: How normal is normal? Dr Nicole Schaeren-Wiemers, University Hospital Basel, Switzerland and Professor Richard Reynolds, Imperial College London Multiple sclerosis is characterised by the presence of discrete areas of demyelination scattered throughout the CNS; with these islands of damage surrounded by normal tissue. Since new lesions would have to appear in this normal area, could examining these areas reveal the earliest changes in the development of MS lesions? The two research groups lead by Dr Schaeren-Wiemers and Professor Reynolds are using a very sensitive technique called “microarray analysis” to look for these changes in so called “normal appearing white matter” in tissue from MS donors. Tissue samples were selected from 10 MS tissue donors and 7 patients that did not have MS. These samples were first examined under a microscope to ensure that the MS tissue did not contain a lesion and that it appeared essentially “normal”; all 17 samples were then introduced into the microarray system. The system can test 3,000 genes in a single experiment! It allows the researcher to identify which of the 3,000 genes have been switched on and which ones turned off in the tissue. These pictures show two microarray slides; the left one received tissue from a control and the right, a sample from an MS donor. Each dot represents one gene; and the darkness of the dot indicates how activated the gene was. When the researchers compared the intensity of dots obtained using the control tissue samples with the normal appearing MS tissue, they found that the activity of 334 genes had changed – in particular, one group of genes that directs the response of cells to stress; and a second group regulating the response of tissue trying to protect itself against damage. These research groups suggest that in the brains of people living with MS, there is a balance between “damage” on the one hand and “defence against damage” on the other. It is when the balance tips to “damage” that a site becomes susceptible to developing a lesion. This work gives rise to a new area of research with the focus on why lesions fail to develop in some areas of normal appearing tissue in MS. Could new therapies look at tipping the balance to help the brain tissue protect itself against damage? 3. Chemical messengers: How do white blood cells breach the blood-brain barrier? Professor Nicola Woodroofe, Sheffield Hallam University, Sheffield Components of the immune system, the white blood cells and antibodies, are thought to be responsible for damaging the myelin and oligodendrocytes (cells that make the myelin) in lesions seen within the CNS of individuals living with MS. An early event in the formation of an MS lesion is one of white blood cells moving from the circulation into the brain tissue. The dissection of this seemingly simple, but actually complex series of events is the task that Professor Woodroofe and her group have set themselves. They are looking at a potent chemical messenger used by the immune system called TNF (the letters stand for tumour necrosis factor - a name that has more to do with how it was discovered than what it actually does). One of the actions of TNF is to act on blood vessel walls in the brain (blood-brain barrier - BBB) to allow the passage of white blood cells across the BBB and into the tissue. The secretion of TNF is caused by the action an enzyme called – ADAM17. In the first series of experiments, Professor Woodroofe’s group have been setting-up a system with which they can accurately detect and locate ADAM17 within the brain. The images below show what is seen when looking down a microscope at tissue slices from an MS patient. The slices have been treated with three different dyes that fluoresce –the wisps of red on the background of purple dots in the picture on the left show the presence of two blood vessels in the tissue slice; and, the one on the right shows that these blood vessels are expressing large amounts of the enzyme ADAM17. TNF is a potent chemical that plays a number of different roles - as well as its effects on the BBB, TNF may also be responsible for demyelination. One way of stopping thedetrimental actions of TNF is to prevent its release by inactivating ADAM17. As a first step Professor Woodroofe’s group is learning more about the presence of ADAM17 within MS lesions. page 4 page 1/ page 2/ page 3 page 4/ page 5/ page 6/
	The UK Multiple Sclerosis Tissue Bank Division of Neuroscience and Mental Health Imperial College London Hammersmith Campus Du Cane Road London W12 0NN Tel: 020 7594 9734 Fax: 020 7594 9735 E-mail: ukmstissuebank@imperial.ac.uk
The UK Multiple Sclerosis Tissue Bank is funded by the Multiple Sclerosis Society of Great Britain and Northern Ireland, registered charity 207495.