Targeting the Type I interferon pathway in Neuromyelitis Optica Spectrum Disorder

视神经肌病是一种神经系统疾病，可导致严重残疾和失明。患者接受广泛的免疫系统抑制治疗。这适用于一些-但不是所有-患者。虽然我们有很好的药物，但目前还没有办法精确预测谁需要哪种药物。因此，这个项目的目的是开发一种新的方法来确定哪些患者将受益于不同的，有针对性的治疗。NMO是由抗体直接攻击水通道蛋白-4引起的，水通道蛋白-4是一种在称为星形胶质细胞的脑细胞表面高浓度发现的蛋白质。这有什么重要的？星形胶质细胞在大脑中起着至关重要的作用;控制水平衡，支持有效的通信，并为其他脑细胞提供能量。在NMO中，星形胶质细胞由于抗体攻击而死亡，并且不能执行这些角色。这会导致炎症和供应手臂，膀胱，肠道，眼睛和腿的神经中的无效通信。一些患有NMO的患者血液中一种称为干扰素的蛋白质水平升高。通常这种蛋白质有助于保护我们免受病毒感染，但它与产生不良的致病抗体有关，如在NMO患者中发现的抗体。我们认为干扰素水平可能提供一种预测哪些患者对靶向免疫治疗有反应的方法。我们的实验室将采用最先进的超精确方法测量患者血液样本中的干扰素。我们将使用这种技术来测量来自英国各地的一组患者的干扰素水平。然后我们将研究干扰素水平与患者疾病严重程度以及患者对治疗的反应之间的关系。与此同时，我们将研究人类免疫细胞和星形胶质细胞，试图了解干扰素如何以及为什么促进免疫系统攻击星形胶质细胞。这可以帮助我们找到其他药物的新靶点。

Neuromyelitis Optica Spectrum Disorder (NMO) is a disease of the nervous system which can cause severe disability and blindness. Patients are treated with broad suppression of the immune system. This works for some -but not all- patients. Although we have good drugs, there is currently no way to precisely predict who needs which drug. So the aim of this project is to develop a new way of identifying which patients would benefit from a different, targeted treatment.NMO is caused by a direct antibody attack upon aquaporin-4, a protein found at a high concentration on the surface of brain cells called astrocytes. What's the importance of this? Astrocytes play vital roles in the brain; controlling water balance, supporting efficient communication, and supplying energy to other brain cells. In NMO, the astrocytes die as a result of the antibody attack and cannot perform these roles. This leads to inflammation and ineffective communication in the nerves that supply the arms, bladder, bowels, eyes, and legs. Some patients with NMO have an increased level of a protein called interferon in their blood. Usually this protein is helpful at defending us from viral infections but it has been linked to production of bad disease-causing antibodies, like the antibodies found in NMO patients.We think that interferon levels may provide a way of predicting which patients will respond to targeted immune treatments. Our lab will be working with a state of the art ultra precise way of measuring interferon in patient blood samples. We will use this technique to measure interferon levels in a group of patients from across the UK. Then we will look at how interferon levels relate to the severity of patient disease and the response that people have to treatment.In conjunction with this we will study human immune cells and astrocytes 'in a dish' to try and understand how and why interferon promotes the immune system's attack upon astrocytes. This could help us to find other new targets for medicines.