Targeting multiple sclerosis
Prof Daniel Altmann
Imperial College London
2007 – 2008 One Year Pilot Study
Functional analysis of the T cell immune response in multiple sclerosis by gene silencing.
Prof Altmann is Professor of Immunology, Head of the Human Disease Immunogenetics Group and Deputy Head of the Department of Infectious Diseases and Immunity, at Imperial College London.
Multiple sclerosis (MS) is the most common disease of central nervous system demyelination, and causes very substantial morbidity and mortality. This devastating disease, for which there is no cure, affects around 2.5 million people, causing a range of symptoms, including muscle weakness, loss of co-ordination, problems with speech and vision, severe fatigue, pain and depression.
The hallmark ‘plaques’ of MS result from demyelination which predominantly occurs during the inflammatory phase of the disease. This is typically followed by a neurodegenerative phase, associated with irreversible axonal loss. There is a widely held view that a key mechanism involves the autoimmune recognition of self myelin antigens by T-lymphocytes.
In a multi-system disease such as MS, much research emphasis has been placed on animal ‘models’ of the human illness. There have been more than 10,000 publications on the induction of the surrogate condition, experimental allergic encephalomyelitis, in rodents, guinea pigs, rabbits and monkeys. Animals suffer inflammation and damage to the nervous system that may result in paralysis, in experiments that can cause distress and suffering. However, it is becoming increasingly possible to generate functional data about the immunology of MS by studying patients’ T-cell responses.
This Dr Hadwen Trust-funded pilot study will characterise the specificity of patient T-cells using a method known as tetramer-guided epitope mapping. The cells will be analysed for patterns of cytokine release and for expression of differentiation markers. RNA knockdown experiments will be used to analyse the effect of molecules on dendritic cells (DC) in autoimmune antigen presentation, focusing on the effects of co-stimulatory molecules of the B7 family. These are experimental questions which have in the past routinely been addressed using knockout mice.