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

我们最近发现了导致湿疹和许多其他与湿疹相关的疾病的主要基因，如过敏和湿疹相关的哮喘。丝聚蛋白基因，使皮肤屏障形成所必需的蛋白质，是完全失活的基因突变，约10%的人口，导致？漏水？允许细菌、过敏原和化学物质等异物进入体内的皮肤。这些外来物质被免疫系统发现，这导致皮肤炎症（湿疹），并作为次要事件，其他系统如肺（哮喘）。聚丝蛋白基因是两种不同类型药物的理想靶点，这两种药物可以拯救某些有缺陷的基因并使其重新启动，或者提高基因的活性。我们已经证明，这些药物确实可以拯救或促进细胞和皮肤中的聚丝蛋白的产生。该基金旨在开发密切模仿人类聚丝蛋白缺陷的动物模型。这将使我们能够剖析疾病机制，重要的是，测试针对该基因的新治疗系统。该项目有可能为英国超过400万人或全球数千万人提供治疗。如果及早服用，这些药物可以预防湿疹和相关疾病的发作，如过敏和某些类型的哮喘和花粉热。

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.