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Therapeutic targeting of the innate immune system in multiple sclerosis

Objective

Multiple sclerosis (MS) is neurological disease that is characterized by clinical attacks of paralysis, loss of sensation, loss of vision, and genito-urinary symptoms. MS affects an estimated 500 000 patients in Europe, at a cost to Europe of over 9 billion euro per annum, and is the most frequent cause of neurological disability in young adults. Women are affected approximately twice as often as men.

The mechanisms of disease are thought to involve a reaction of the immune system against components of the brain and spinal cord (autoimmune disease). MS is currently treated with drugs that regulate the immune system. Of these, the most frequently used is Interferon-beta (IFNb), a molecule that was initially discovered for its antiviral properties and was subsequently found to be immunomodulating. The technology for the production and purification of recombinant IFNb significantly contributes to the healthcare cost. IFNb can be produced in large amounts by the human immune system, particularly during viral infections.

The innate immune system has the capacity to recognise structural components that are shared by viruses, bacteria, and other infectious agents, via cell surface molecules called Toll-like receptors (TLR). In experimental autoimmune encephalomyelitis (EAE), an animal model of MS, we have successfully treated the disease by administering TLR ligands and inducing endogenous IFNb and related molecules. In this translational research project, we are planning to transfer this treatment strategy to MS patients. The overall objective of this project is to make therapeutic use of the innate immune system's ability to produce endogenous interferons, cytokines, and chemokines in MS.

TLR agonists will be developed for clinical testing, with the expected benefits to the European Union being:
a) a novel strategy for MS treatment;
b) a significant reduction in treatment costs; and
c) improved quality of life for MS sufferers.

Call for proposal

FP6-2004-MOBILITY-12
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Coordinator

UNIVERSITY OF NOTTINGHAM
EU contribution
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Address
University Park
NOTTINGHAM
United Kingdom

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