In vivo model systems to develop filaggrin as a drug target in atopic disease

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We recently discovered the major gene that causes eczema and a host of other conditions associated with eczema, such as allergies and eczema-associated asthma. The filaggrin gene, which makes a protein essential for skin barrier formation, is completely deactivated by genetic mutations in about 10% of the population, leading to ?leaky? skin that allows foreign material such as bacteria, allergens and chemicals to enter the body. These foreign substances are seen by the immune system and this leads to inflammation of the skin (eczema) and as a secondary event, other systems such as the lungs (asthma). The filaggrin gene is an ideal target for two different types of drugs that can eithr rescue certain defective genes and switch them back on again, or boost the activity of a gene. We have shown that these drugs can indeed rescue or boost filaggrin production in cells and skin. This grant is designed to develop animal models that closely mimic the human filaggrin defects. This will allow us to dissect out the disease mechanisms and importantly, to test the new therapy systems aimed at this gene. This project has the potential to treat over 4 million people in the UK, or 10s of millions worldwide. If administered early, such drugs could prevent the onset of eczema and associated diseases, such as allergies and certain types of asthma and hay fever.