This is to let you know about a research project based on a novel idea of how MS develops. I am a pathologist, and have spent most of my career on medical research. I am returning to researching on MS after a long period of working on the arterial disease that causes heart attacks and strokes. The reason for my return to MS work is that I believe that MS may develop in a way similar to arterial disease when the details of the process, the molecules concerned, are considered.
I have sent a grant application to the MS Society to support this work. Also I have been able to start it right away with the help of QMUL science students doing laboratory projects.
In arterial disease, the particles carrying fats through the blood to all parts of the body become lodged in the walls of arteries. There the fats in them degrade, and it is known that they are then treated by the body as foreign. As a consequence an inflammatory response develops, in which white cells from the blood accumulate. The walls of the artery then thicken, so much so that the flow of blood is impeded, and supply to vital organs such as the heart is diminished.
In the brain, there is much fat in the myelin covering of nerves. In MS, this nerve coating and the cells making it are attacked by inflammation. Other researchers have found that there is an immune response against damaged fats in MS. This has been found in the fluid surrounding the brain, the cerebrospinal fluid.
Furthermore, one particular type of antibody immune response against damaged fats predicts a severe future course of the disease. I therefore propose that some initial local damage to the myelin coat of a nerve, perhaps by a common or transient infection, results in the formation of damaged fats in the brain. Then in individuals that are predisposed, perhaps for genetic reasons, an immune response is generated against the damaged fats. It is known that some immune responses generate disease rather than protect against it, and in MS more damaged fats may be formed. So this response itself may result in more local damage to the myelin and in this way an expanding MS plaque develops in the brain. It is interesting that both arterial and MS disease grow in a similar way as expanding local plaques.
The research project is in two parts. At the moment we are testing samples of cerebrospinal fluid from MS patients, obtained from the MS Brain Bank, for an immune response of antibodies to damaged fats. We have developed a straightforward assay for this. Later we shall look using powerful microscopic techniques for the presence of the damaged fats and the immune response against them in MS. This will be done in brain tissue, particularly in the MS plaques. The tissue has been obtained from MS patients who have died and donated their brains to the MS Tissue Bank.
The significance of this research is that if it is successful, it will help the understanding of how MS develops. This will mean that the direction of work on the development of drugs can be focused better. Already it fits with recent developments, as drugs designed to destroy the cells that make the antibodies are effective in some people with MS. The assay we are currently developing may be useful in the diagnosis of MS and the prediction of its future course.
by Dr Robin Poston, Centre for Microvascular Research, William Harvey Research Institute, Queen Mary University of London.
Dr Robin Poston is a pathologist who has spent much of his career in research, and has worked on atherosclerosis almost throughout. He was a student at King’s College, Cambridge University, where he first studied physical sciences and then medicine. Clinical training followed at the Middlesex Hospital, London, where he joined the Immunology laboratory at the Middlesex Hospital Medical School to start research on the immunology of atherosclerosis. Subsequently he was appointed a Lecturer in the Department of Pathology, Guy’s Hospital Medical School, and in 1979 presented some of the early ideas about atherosclerosis as an inflammatory disease to the Royal Society of Medicine.
At Guy’s Hospital, he trained as a pathologist in immunology and histopathology, and in the 1980s set up a diagnostic immunohistochemistry service. In 1992-6 he published seminal work on the involvement of leukocyte adhesion molecules in atherosclerosis: his paper on ICAM-1 has been one of the most cited in the American Journal of Pathology. For this study he introduced colour image analysis, which since has been used extensively for the quantitation of histological research. Other fields of research around that time were multiple sclerosis and asthma.
Teaching of medical students was another extensive facet of his work, and he organised many pathology courses. In 2004 he set up the Graduate and Professional Entry Course for the medical school of King’s College London, which involved compressing the normal first two years of teaching into one.
In 2008 he moved to the William Harvey Research Institute of the Barts and the London Medical and Dental School, part of Queen Mary University of London. Although now officially retired, he continues with research on atherosclerosis, and recently again on multiple sclerosis.